Category Archives: MTHFR

To Health With That! MTHFR Podcast

Have You Listened To The Amazing MTHFR Podcast Yet?

I started a podcast, which has been a strange and wonderful journey. It’s all about MTHFR because you know that is a passion project for me. I know how much managing my compound heterozygous situation has done for me, and I want to pass on all of that knowledge to you.

The Risks of High Dose Folate To Health With That! MTHFR Mutations.

Folate is a great thing – it's vitamin B9 and your body needs it to make new cells, replicate DNA, and so much more. But there are risks of too much folate, so how much folic acid is too much? And how dangerous is it to take high dose folic acid over time? The research exists for high dose folic acid, but what about L-5MTHF, or methyl folate? Does high dose methyl folate have the same risks as high dose folic acid? We have so many questions, and very few definitive answers, but there is lots of information that we do have. This episode of the To Health With That! podcast will cover the risks of high dose folic acid, the risks of high dose methyl folate, the risks of high dose L-5MTHF, and what we do and don't know from the research. Thanks for watching! Here are some other links that you might like. Genetic Rockstars – a community for people making the most of their favorite genes and getting better together (first month free for YouTubers!): https://community.tohealthwiththat.com/plans/204575?bundle_token=4da8ed9c5f00a92363bcd15ad2ac26dd&utm_source=manual FREE MTHFR Basics course: https://courses.tohealthwiththat.com/p/mthfr-basics I would appreciate it so much if you would support this channel by using affiliate links when you buy supplements and resources (I heart you!): Seeking Health:  https://bit.ly/3afXYH4 Amazon: https://www.amazon.com/s?k=Health+best+sellers&i=stripbooks&camp=1789&creative=9325&linkCode=ur2&linkId=29fff6e3ea954499d2eed32d46428454&tag=tohealthwitht-20 Queen of The Thrones Castor Oil Packs:  https://shop.queenofthethrones.com/amy-tohealthwiththat  For 10% off any order of $59 or more, use the code AMY_TOHEALTHWITHTHAT10
  1. The Risks of High Dose Folate
  2. What's Happening With The THWT Podcast in September?
  3. Gentle Six Week Detox For MTHFR
  4. Heal Your Adrenals – Part Two
  5. Heal Your Adrenals – Part One

This MTHFR Podcast is Called To Health With That!

We’re doing a deep-dive into MTHFR issues in small bites of 10 minutes or less because it’s easier to learn things in small layers. Not sure what MTHFR is? Here’s a couple of links to get you started: MTHFR basics, MTHFR in the simplest terms possible – it’s the magic chair.

I would love your feedback, so if you have any comments, suggestions, or words of wisdom, shoot them to me!

To Health With That! MTHFR Podcast
The Podcast is HERE!!!

3 Ways to Practice Meditation

practicing meditation is beneficial for anxiety, depression, insomnia, MTHFR, and high blood pressure
Start your meditation practice today with the free resources below – it’s especially helpful for people with anxiety, depression, insomnia, blood pressure issues or MTHFR mutation.

If you, like me, meditate, you can likely go on and on about how much meditation helps you. After all, practicing meditation has been scientifically proven to aid in pain management, improve focus and motivation, and reduce the symptoms of anxiety and depression. But, did you also know that practicing meditation can help ease the symptoms of genetic diseases such as MTHFR. Now, before your mind gets away with you, yes, that is an actual condition, and its full name is methylenetetrahydrofolate reductase.

MTHFR is the name of a gene (one of 20,000). 30% to 50% of all people actually carry an MTHFR gene mutation. This puts people with the mutation at a higher risk for heart disease, Alzheimer’s, stroke, and cancer. Some symptoms of MTHFR are:

  • Cardiovascular disease
  • Migraines
  • Chronic fatigue
  • Hormonal issues
  • Autoimmune and thyroid disease
  • ADHD

Adjusting your diet can help improve your symptoms, as can mindfulness and meditation. Meditation helps to calm your mind and focus on the now to reduce dwelling on the past or worrying about the future. By easing your stress and anxiety you can lower your body’s blood pressure, reduce memory loss, and new studies have shown that practicing meditation can actually reverse genetic DNA reactions that cause stress. Here are three different types:

Zen Meditation

Zen meditation dates back over 1,300 years and is a traditional Buddhist discipline. The purpose is to uncover the clarity and workability of the mind. Zen meditation involves observing the world around you and letting go of the thoughts and feelings within your mind. It has proven especially important to help people sleep better by mimicking the REM sleep cycle and overcoming anxiety and stress-based sleeping disorders such as insomnia. Zen Mountain Monastery provides detailed Zen Meditation (Zazen) instructions here.

Mindfulness Meditation

Mindfulness is similar to Zen, but instead of the general openness, mindfulness meditation teaches you how to be mindful, or aware, of your thoughts and perceptions at any time whether you are in a meditative state or not. Mindfulness helps you learn to remain relaxed at all times or find relaxation when you need it. This allows you to stay focused and to find clarity even in stressful times. Mindfulness has been the most beneficial type of meditation for me, but everyone is different and it is important to find the right fit for you.

Guided Meditation

Guided meditation is led by an individual. Through the guidance of a teacher, this form helps you to focus and concentrate at a higher level as well as provide significant clarity faster which is helpful in visualizing weight loss, quitting smoking, and other obstacles. In addition to benefits shared with other forms of meditation, guided meditation helps to improve your overall visualization skills as well as build a stronger connection between your left and right brain hemispheres. UCLA Mindful Awareness Research Center has a number of free guided meditations in both English and Spanish, as well as an app.

Practicing meditation can help your physical and mental health, especially with MTHFR mutations.
Practicing meditation can help your physical and mental health, especially with MTHFR mutations.

Practicing meditation can help you relax your mind and spirit. This can help reduce pain, anxiety, depression and even blood pressure. For us MTHFR folks, reducing anxiety and pain can be a godsend. Especially for people who are not able to take methylfolate, or for people who notice that methylfolate makes their depression worse. While all forms of meditation are similar, Zen, Mindful, and Guided meditation have different focuses and different feels. If you are new to practicing meditation, try different types to find the one that feels best and most helpful for you.

Taurine for Gallbladder Sludge and Stones

Taurine is used for many things, but taurine for gallbladder sludge doesn’t get the attention it deserves.  It’s well known for energy, of course, hence every energy drink out there. While increased energy is a *really* great side-effect, anyone with gallbladder sludge can tell you that getting rid of that is pretty good too.

Taurine is great for gallbladder sludge, and also common in energy drinks (not that I'm suggesting energy drinks for your gallbladder - that wouldn't work out). Great photo by Brekingpic on Pixels.
Taurine is great for gallbladder sludge, and also common in energy drinks (not that I’m suggesting energy drinks for your gallbladder – that wouldn’t work out). Great photo by Brekingpic on Pixels.

Why Does Taurine Help With Gallbladder Sludge and Stones?

So, why does Taurine help with gallbladder sludge and also help to decrease gallstone formation? Great question. The substance we generally call “bile” in the gallbladder is actually a conjugated bile salt. Primary bile acids are made in your liver, then conjugated (which means bonded to) either taurine or glycine to become active bile salts. Meaning, without the taurine or glycine, they don’t do anything at all. If you want more detail about this process, there is a great article here. Taurine and glycine are both common in the Standard American Diet, especially from meat and fish sources and also can be made by our bodies if we’re low. So, what is the problem?

Common Factors that Decrease Available Taurine

This is the part that gets us in trouble, because many of the factors that decrease Taurine are ALSO risk factors for developing gallbladder sludge and stones. Are you noticing a pattern here? Here are some common taurine drains:

  • MSG. Dietary MSG requires taurine for metabolism and excretion.
  • High Estrogen. People with high estrogen use so many of their methyl donors trying to deal with estrogen, that there are none left to help their bodies make taurine (especially methionine). High estrogen, you will recall, is also one of the primary risk factors for gallstones and gallbladder sludge.
  • MTHFR Mutation. Sorry MTHFR folks – I feel your pain. MTHFR mutations also mean there are fewer methyl donors, hence lower taurine production and also lower estrogen clearance. Healthy bile is methylation-dependent.
  • Diabetes. There is a link between diabetes and low taurine (and also taurine has been shown to reduce blood sugars).

The Best Way to Supplement Taurine

While energy drinks are fun, these are NOT the best source if you’re trying to prevent gallbladders sludge or stones. See the diabetes thing above? Yeah. Energy drinks typically have a hefty dose of sugar and aren’t going to help your health at all. Food sources of taurine are great in moderation and as part of a healthy diet – meats, dairy products and fish are all high in taurine, but they are also often high in cholesterol, which is best taken in moderation with gallstones or gallbladder sludge. That leaves supplements, which are probably the best option for therapeutic doses of Taurine for gallbladder sludge and stones. Typically suppelements are dosed in 500 or 1000 mg pills and you can take up to 3000 mg daily without harm, even long term. For more information on Taurine or safe dosing, read this.

What Else Should I Be Doing?

While you’re taking your taurine, it’s important to remember to moderate cholesterol in your diet (but not eliminate it – healthy gallbladders need dietary fats to contract and clean themselves out). It’s also incredibly important to remember to get great water intake because, without water, you’re not flushing anything out of anywhere. Also, increase your fiber intake. Fiber not only helps to eliminate fats and bile salts in the intestines but also, helps to pull out estrogens, which decrease taurine. Taurine will help you to be sludge (and pain) free.

Get sober. MTHFR and alcohol are linked - find out how.

Getting Sober – MTHFR and Alcohol

Healthy Habits to Maintain Sobriety and Truly Live in Recovery from MTHFR and Alcohol.

Article by Michelle Peterson at recoverypride.org, in honor of April – Alcohol Awareness Month

Making the decision to get clean and sober is only the first step to a healthier life. Once you are in recovery for addiction, you may find that you still lack energy or emotional balance, or the original issue that you were self-medicating is still present. The reality is that it takes more than quitting substances to feel your best. Replacing the unhealthy habits of substance abuse with new healthy habits will not only help you get back to your true self, but it also helps maintain sobriety. If you, like many others seeking recovery, have an MTHFR mutation, then addressing this issue will help in your overall progress. After all, MTHFR and alcohol are linked.

Set a Fitness Goal

It’s no secret that regular exercise is essential for good health, and for someone in recovery, it is one of the absolute best ways to get stronger, both physically and mentally. Addiction takes a toll on your body, which can lead to poor health and a general lack of energy. Simply being active on a regular basis counteracts these feelings, builds strength, and can even reverse poor health. Start out slow, and for the best success in making exercise a habit that sticks, try different activities to find something you really enjoy.

Exercise, especially exercise involving the great outdoors, can help boost health in MTHFR and alcohol abuse or recovery. Thanks for the lovely picture  by Hoang Nguyen Xuan from Pexels

Exercise, especially exercise involving the great outdoors, can help boost health in MTHFR and alcohol abuse or recovery. Thanks for the lovely picture by Hoang Nguyen Xuan from Pexels

Getting in the habit of regular exercise packs a one-two punch in helping contribute to recovery. Along with the physical effects you see and feel, being active also improves your mental health, and mental health is key in both MTHFR and alcohol issues. Managing emotions is crucial for maintaining sobriety, and exercise has been shown to increase the feel-good chemicals in your brain and give you an amazing boost in self-confidence. Look to other inspiring people who have found exercise to help in recovery, such as this Ironman athlete, who was featured by CNN. You don’t have to do an Ironman race, but set a goal to work toward, which will help keep you on track and give you a sense of accomplishment.

Fuel Your Body and Mind

Having a balanced, healthy diet helps you feel better both physically and mentally throughout recovery. It’s common for those in recovery to have nutritional deficiencies, so focus your diet on eating plenty of foods packed with nutrients you need. A good general rule is to eat the rainbow, which means eating plenty of fruits and vegetables of all colors in order to get a full variety of nutrients. While good nutrition makes you stronger and boosts energy, Harvard Health Publishing explains how a diet high in unhealthy fats and sugar can impair brain function and make symptoms of anxiety and depression worse. One of your primary goals in recovery should be to manage stressors and overall mental health to avoid relapse, so the emotional effects of a poor diet are the opposite of what you need.

Manage Your MTHFR

Not only does MTHFR mutation increase the likelihood of alcohol overconsumption, it also makes the nutritional impact of alcohol worse.  Alcohol is known to deplete several B vitamins in the body including folate (this is us, MTHFR folks), thiamine, Riboflavin, B6, B12 and vitamins A, E, D and K. In addition to a healthy diet with a rainbow of colors, it is a good idea to supplement B vitamins and methylfolate to bring those levels up to par. This is doubly important if you have a known or suspected MTHFR mutation. Because MTHFR mutations often affect neurotransmitter levels, it is important to start supplementing methylfolate the right way, because taking too much can cause negative symptoms.

Discover a Passion

Exercise and nutrition are the foundations for a healthy body and mind, but you need more in your life to truly thrive. Now is the perfect time to start a new hobby or rediscover a passion from your past. When you’re no longer being controlled by substances, your mind is freed up to discover creativity. Learning a new skill and throwing yourself into a creative endeavor can be incredibly rewarding in recovery. You may enjoy making something with your hands, such as knitting, pottery, or woodworking. This type of hobby adds value to life and can also be a strategy for coping with stressors and triggers.

You may want to find a hobby that involves getting outdoors. This can be anything from taking regular walks in your neighborhood, perhaps with a friend, to outdoor adventures like hiking, mountain biking, or kayaking. Being outdoors, especially if you’re doing something active, is a habit that benefits your health in multiple ways. The vitamin D from the sun is great for your mood, and connecting with nature is grounding.

Finding a new hobby and making that part of your daily life is like icing on the cake when it comes to new healthy habits. When you’re in the throes of substance abuse, caring for yourself is the last thing on your mind, and it’s easy to get away from doing things you really love. Staying committed to recovery requires caring for your physical and mental well-being, and starting these healthy habits helps you accomplish that goal while giving life meaning.

 

MTHFR and Birth Control Pills. Ugh.

Naturally, MTHFR and birth control pills interact – it’s not like this is an easy mutation to live with in other senses, why would it leave our contraceptive options untouched? Complaining aside, I could have saved myself years of miserable experiences with the pill if I had known this.

MTHFR and birth control pills is a bad combination. Photo by Bryancalabro.

MTHFR and birth control pills is a bad combination. Photo by Bryancalabro.

Birth Control Pills Deplete Folate in Your Body

If you’re familiar with MTHFR mutations, then you’ve probably already figured out why this is a no-win situation for us MTHFR gals, but if you’re not then read on. Birth Control Pills are known to deplete folate levels in women and have been known to do so since the ’80s.  This is a problem for all women, but especially those who have compromised folate metabolism in the first place (ahem, that’s us MTHFR folks). This folate depletion is part of the reason for some of the most common side effects of birth control pills – fatigue, mild depression, even acne.  It’s also linked to an increased risk of neural tube defects in babies born to women who have recently stopped using birth control pills.

Due to the risk of neural-tube defects in women who become pregnant after recently stopping birth control pills, a new folate-fortified pill called Beyaz ® has been developed.  In good news, it is supplemented with an active form of folate so if you’re an MTHFR gal and you absolutely must take oral contraceptive pills, this one might be a good option for you.

If you don’t tolerate birth control pills and can’t figure out why, it could be because you have an MTHFR mutation – especially if you have signs of a folate deficiency even though you’re taking your birth control pills WITH a multivitamin or folate supplement.

Birth Control Pills also deplete B12, Magnesium and other nutrients

Not only is folate depleted, but its partner-in-crime B12 is depleted too.  B12 is also highly involved in the methylation cycle, and again this can be an issue for MTHFR folks (especially those with the related MTRR mutation) as well.  Nutrients to watch when taking birth control include:

  • Folate
  • B12
  • Magnesium
  • Vitamin C
  • B2 – Riboflavin
  • B6 – Pyridoxine
  • Zinc
  • Vitamin E
  • Selenium

Of course for MTHFR folks the folate is the biggest factor, but folate always works in tandem with other B vitamins so make sure you’re getting a good B complex supplement if you do choose to take birth control pills.

Birth Control Pills May Also Affect Serotonin Metabolism

In related bad news, Birth control pills may also affect your Serotonin metabolism (which might also be compromised in MTHFR folks because of this.)  This study, published in the Journal of Ayub Medical College, showed that there was a difference in serotonin levels between non-contraceptive users and oral contraceptive users that was statistically significant in pre-analysis but not statistically significant in post-analysis. That means that although there was a difference in the two groups, it wasn’t large enough that we can say with confidence that it wasn’t chance.  There was, however, a significant difference in serotonin levels for those using injectable contraceptives. Injectable contraceptives are a bad idea on so many levels, but let’s add this as another reason not to use them.

What Type of Contraceptive is Best for MTHFR Mutants?

Completely safe relative to MTHFR mutation types (other risks though – do your research!):

  • Condoms, Female Condoms
  • Copper IUD (non-progesterone secreting)
  • Vasectomy or tubal ligation

If you feel you must take hormonal contraception:

  • Use the lowest dose of hormone possible and make sure you’re adding extra supplements to counteract nutritional deficiencies. Consider Beyaz® but remember if you’re an MTHFR mutant you might still need additional active folate, and it doesn’t supplement any of the other nutrients it depletes so you’ll also need those.
  • Avoid using injections, pellets or implants simply because once they’re in you can’t get them out.  That means if your body doesn’t tolerate it you’re stuck with the side effects until the dose wears off.
  • If you’re considering getting pregnant, please stop all oral contraceptives at least a year before you start to try and make sure you work diligently during that year to boost your levels of all of the nutrients that may have been depleted.

 

MTHFR C677T Superpower: Prostate Cancer Protection.

There could be benefits of MTHFR C677T mutation. Who knew? © Patrimonio Designs Limited | Dreamstime Stock Photos

There could be benefits of MTHFR C677T mutation. Who knew? © Patrimonio Designs Limited | Dreamstime Stock Photos

I am so happy to report that the MTHFR C677T mutation now comes with a superpower, and it’s prostate cancer protection.  It’s not quite X-Men worthy and I have to admit mind control might be a bit cooler, but protection against one of the most common forms of cancer is nothing to scoff at.

The association between MTHFR mutation and prostate cancer has been unclear, with some studies showing increased risk, some studies showing no change and some showing decreased risk, so the information can be difficult to wade through. A recent research study conducted in Shanghai and published in Scientific Reports shows that C677T polymorphisms, whether they are homozygous or heterozygous, are actually protective against prostate cancer although they are quick to say that this study was conducted on the Han Chinese population in Shanghai and that the results may be different for different ethnic groups.

The study shows that intracellular homocysteine levels are slightly elevated when the C677T mutation is present and that elevated homocysteine actually helps to encourage damaged cells, such as precancerous and cancerous cells, to die off the way they should, rather than proliferating into full blown cancer. In unfortunate news, a recent meta-analysis published in Genetics and Molecular Research, showed that this association may not exist in caucasian males and that in this population C677T mutation may not have any effect on prostate cancer. Interestingly, this same meta-analysis showed that the A1298C mutation might have a slight protective effect against prostate cancer in European males.




The most important thing to remember, is that almost every mutation that exists in humans or animals has a double edge – it often has some drawbacks, but typically benefits too or the members of the population with that mutation would die out.  MTHFR seems to be, if anything, becoming more common so I suspect in years to come we will find many other benefits associated with it.



Am I Overmethylated? MTHFR Questions.

Overmethylated vs. undermethylated seems to be one of those things that everyone defines a different way, so let’s talk about it and see if we can bring some clarity. The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them.  These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation).  Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Overmethylation MTHFR

This is less common than undermethylation. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Overmethylation in this context means that the methylation cycle as a whole is sped up, or downstream reactions that use SAMe (the ultimate product of the methylation cycle) are compromised in such a way that there is too much SAMe floating around wanting to methylate something.

  • Clinically overmethylators are more likely to have agitated or anxious conditions. Frequently panic or anxiety attacks (64% of panic/anxiety clients at the Walsh Research Institute), paranoid schizophrenia (52% of paranoid schizophrenic clients at WRI were overmethylators), ADHD (28%), behaviour disorders (23%), depression (18%). Depression  can occur in under, normal or over methylators but 18% of depressed clients of Dr. Walsh are overmethylators.
  • Mutations most likely to contribute to overmethylation are AGAT, GAMT, CBS and MT. MTHFR mutation usually pushes towards undermethylation (but I myself am compound heterozygous MTHFR and an overmethylator) Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.
  • Other contributing factors are impaired creatine synthesis. This is because Approximately 70% of the SAMe from the methylation cycle is used by creatine synthesis, so if this is impaired the SAMe is used more slowly. This can be due to genetic factors (AGAT or GAMP) or due to deficiencies of arginine or glycine. Also impaired cystathione synthesis, or other polymorphisms in methyltransferase SNPs that account for the rest of the SAMe use.
  • Overmethylation leads to excessively high activity of dopamine, norepinephrine and epinephrine in the brain.

    If this reminds you of you, you could be overmethylated. A photograph of Robin Williams taken by Michael Dressler in 1979, later used as a cover photo for Time magazine to highlight Williams.

    If this reminds you of you, you could be overmethylated. A photograph of Robin Williams taken by Michael Dressler in 1979, later used as a cover photo for Time magazine to highlight Williams.




  • Symptoms and traits of overmethylation include:
    • High anxiety
    • Sleep disorder
    • High energy, restless, must move and fidget
    • Verbose or talkative
    • Often high artistic or musical ability
    • Antihistamine intolerance (makes anxiety or restlessness worse)
    • Overly empathetic with others
    • Non-competitive in sports
    • Tendency towards food and chemical sensitivities
    • Less likely to have seasonal allergies
    • Histamine Intolerance (or HIT – this is essentially a food sensitivity to high-histamine foods)
    • Low libido
    • Dry eyes and mouth
    • Adverse reaction to SSRI drugs, SAMe or methionine (typically all make anxiety or depression much much worse.
    • An easy way to picture this type is by using Robin Williams as an example.

Is Overmethylated the Same as Over-supplemented?

No, although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might  be “overmethylated” if you are taking too much 5-MTHF or SAMe.  I feel that these are different things entirely.  If you have a tendency to be overmethylated then certainly you would probably feel worse taking something like SAMe, but even without that you are still an overmethylator (in my opinion).  Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Overmethylated. Now What?

Interestingly the best way to balance the consequence of overmethylation, is still 5-MTHF.  This seems strange, because it is also the answer if you’re’ undermethylated, but the effects are actually coming from a different mechanism. Folate actually reduces activity at serotonin, dopamine and norepinephrine synapses. 5-MTHF is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement.  Trouble taking the supplement is surprisingly common, although I think less common clinically in overmethylators (in my experience) than in undermethylators. Niacin or niacinamide can also be helpful for overmethylators as they quench some of the excessive methylation. Again, start slowly.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period.  Here’s a whole post on it.  Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.



Methylfolate Makes Depression WORSE! How Is This Possible?

Finding out you have an MTHFR mutation can be exciting, in it’s own strange way, because all of a sudden there is hope that you can actually help yourself and fix how you’re feeling, so it really feels like being kicked in the gut if you start taking 5-LMTHF and the methylfolate makes depression worse.  Have no fear, there is an explanation and also some possible solutions. Read on my friends.

Methylfolate makes depression worse! Don't worry - there is a solution. Great photo by © Philippe Ramakers | Dreamstime Stock Photos

Methylfolate makes depression worse! Don’t worry – there is a solution. Great photo by © Philippe Ramakers | Dreamstime Stock Photos

Why Does Methylfolate Make Depression Worse?

We recently talked about the terms “undermethylated” vs. “overmethylated” and although there aren’t great lab tests to show your status, typically you can determine your general tendency through their symptom picture.  Depression, however, can be ambiguous because it can happen in people who are undermethylated, overmethylated or people with totally normal methylation.  Although having the MTHFR mutation pushes many people into the undermethylated category, having the mutation itself isn’t enough to tell you if you’re under, over or normal. I myself am a compound heterozygous MTHFR mutant, but happen to have other genetic factors that make me an overmethylator – go figure.




5-L methyltetrahydrofolate (5-LMTHF) is suggested for everyone with a methylation issue – over or undermethylators.  It’s the first line of defence because it can actually help both groups to balance their methylation in different ways.  Also for depression specifically, folic acid or 5-LMTHF supplementation can be extremely helpful even without a known methylation issue because folate deficiency is a common cause of depression – so really for most people folate is beneficial. There is one group, however, who doesn’t respond well at all that that is undermethylated people with depression.

Let me clarify – anyone starting 5-LMTHF for the first time, or even increasing a dose, may notice some side effects for the first few days.  Starting to methylate differently can be messy and so this first few days isn’t enough time to know if you actually have a bad reaction. This is why we talk so much about starting with a low dose and easing your way up. If you’ve started with a low dose and you’re easing into it, but your depression gets worse and stays worse beyond the first week or so, then chances are you have undermethylated depression. This means methylfolate, folic acid and even folate rich foods are probably always going to make your depression worse.    Here’s why:

The link between Methylfolate and Serotonin

This is complicated because typically boosting your methylation cycle also helps your body to make more neurotransmitters via BH4 (we don’t need to go into it, but if you want a refresher you can read about it here). So 5-LMTHF is supposed to fix depression by boosting levels of serotonin, dopamine and other key neurotransmitters.  The problem is that 5-LMTHF, folic acid and folate all have a second effect on neurotransmitters, which is to depress serotonin through an epigenetic mechanism.

Epigenetics is essentially the study of how external factors (like nutrition, stress, oxidative damage, etc…) influence the way our genes express themselves. Folate and folic acid, according to the Walsh Research Institute, have an epigenetic effect on the SERT transporter.  The SERT transporter helps to reuptake serotonin after it’s been released. SERT is the target for many pharmaceutical antidepressants (SSRIs, or Selective Serotonin Reuptake Inhibitors). SSRIs work because they interfere with SERT and so serotonin stays active longer, which means you get more benefit from this happy neurotransmitter. Methylfoate, folate from foods and folic acid, while they increases serotonin production through BH4, also increase SERT via an epigenetic effect.  This means they help your brain to clear out serotonin faster, thereby reducing the amount of serotonin that is available for you to use. Essentially this makes folate the anti-anti-depressant.  Sigh.

As a brief reality check – Walsh Research Institute is convinced this is happening (see the link to their presentation above), many MTHFR websites are convinced this is happening, and it certainly explains a lot of what I’ve seen clinically, but for whatever reason I can’t find any published research that says definitively that this is happening so please take this with a grain of salt.

Methylfolate Makes Depression Worse For Me – Now What?

Don’t worry – you have a couple of options.  If you’re sure this isn’t just your body adjusting to methylfolate (the symptoms last beyond the first week of moderate supplementation) then it’s time to check to see if you fit the profile of an undermethylator. If that sounds like you, and your depression is getting worse, then let’s look at your choices.

  • SAMe – Ultimately the end product of the entire methylation cycle is SAMe, so it can be a helpful work around for people who can’t take 5-LMTHF.  This is where all that methylfolate is going and although it doesn’t entirely cover the necessity for methylated folate, it does help with the depression. This is partly because SAMe is a very slow acting serotonin reuptake inhibitor – just like the pharmaceutical drugs only much less powerful. As with any methylation issue, start with a low dose and work your way up.
  • Methionine – This amino acid is a direct precursor to SAMe in the body, and uses the MATI/II enzyme (coded by the gene of the same name) to go through the conversion.  Because this turns into SAMe it can be a much more cost effective way to get the same benefits, which again is as a slow acting serotonin reuptake inhibitor.  The only situation in which that isn’t going to be helpful is if your MATI/II gene has an issue or something is interfering.  Most people find methionine to be effective though, so this can be a far less expensive solution. Again, start with a lower dose and work your way up.
  • St. John’s Wart – This has nothing to do with methylation, only with serotonin.  Happily, St. John’s wart shows similar effectiveness to SSRI medications for major depressive disorder, with significantly fewer adverse events.  Here’s the research study, from the Annals of Family Medicine that compares St John’s Wart (referred to by it’s latin name, hypericum) with SSRIs and other anti depressant medications as well as placebo. Go nature!

It should be said that while SAMe and Methionine will help to augment the methylation cycle, they still aren’t providing folate of any kind, so they won’t protect against the more folate dependent issues like neural tube defects in babies and issues with pregnancy and fertility.  If you have undermethylated depression and are considering getting pregnant it is vital to work closely with a doctor who can help you to get the folate that you need and also help you to offset the depressive symptoms that might come with that. Even though methylfolate makes depression worse,  in pregnancy it might still be necessary so please consult a physician.



If This Sounds Like You, You Might be Undermethylated

MTHFR mutation discussions can quickly turn into Greek and the topic of overmethylated vs undermethylated MTHFR is one of the Greekest. It seems like no two resources on the internet are talking about the same thing when they talk about it and so overmethylation and undermethylation are strange, kind of meaningless words because at the end of the day it feels like nailing jello to a wall. So let’s see if we can sort some of this out.

Whose Idea Is This? I’m Following The Walsh Research Institute

The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them.  These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation).  Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Undermethylation MTHFR

This is the most common state. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Undermethylation indicates that the methylation cycle as a whole is slowed down enough that the end product, SAMe, is typically inadequate and thus causes symptoms.

  • Clinically undermethylators are more commonly autism spectrum (98% of autism spectrum clients at the Walsh Research Institute), antisocial disorder (95% of antisocial clients at WRI were undermethylators), schizoaffective disorder (90%), oppositional defiant disorder (85%), anorexia (82%), and depression (which can occur in under, normal or over methylators but 38% of depressed clients for Dr. Walsh are undermethylators).
  • Mutations most likely to contribute to undermethylation are MTHFR (C677T especially, but also A1298C), MS, BHMT, MAT and SAHH. Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.
  • Other contributing factors are histamine overload and protein deficiency, as well as frank deficiency of folate.

Highly competitive? You might be undermethylated

Highly competitive? You might be undermethylated




  • Symptoms and traits of undermethylation include:
    • Strong willed
    • Highly competitive at sports or whatever matters to them
    • Obsessive/compulsive tendencies
    • Addictive tendencies (more likely to be addicted with less exposure than a normal methylator)
    • High sex drive
    • Tend towards high accomplishment and usually a high achieving family
    • Appear calm and well controlled (possibly over-controlled) but inner tension is high
    • Greater likelihood of seasonal allergies
    • Higher fluidity of tears, saliva, etc…
    • Perfectionist
    • Less likely to be compliant with therapies

Addictive behaviour? You could be undermethylated. © Francesco Bisignani | Dreamstime Stock Photos

Addictive behaviour? You could be undermethylated. © Francesco Bisignani | Dreamstime Stock Photos

Is Undermethylated the Same as Under-supplemented?

No! Although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might still be “undermethylated” if you aren’t taking enough 5-MTHF.  I feel that these are different things entirely.  If you have a tendency to be undermethylated then certainly you will probably need to take 5-MTHF, but even once you’re taking enough you are still an undermethylator (in my opinion), you’re just taking the right protocol.  Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Undermethylated. Now What?

Absolutely the best way to enhance the methylation cycle is by taking 5-MTHF, or 5-L methyltetrahydrofolate.  This is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement.  Trouble taking the supplement is surprisingly common, typically it is an adjustment reaction to actually enhancing the methylation cycle because this changes neurotransmitter levels, encourages detoxification and encourages more than 80 reactions in the body that are methylation dependent. So some adjustment reaction when you’re first taking 5-MTHF is normal and actually a good sign that things are changing in your body.   There is one BIG EXCEPTION TO THIS, and that is if you are undermethylated and have depression.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period.  Here’s a whole post on it.  Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.

HELP! I’m An Undermethylator and I Have Depression.

My next post is going to be all about this because UNDERMETHYLATORS WITH DEPRESSION DUE TO LOW SEROTONIN CAN’T TOLERATE 5-MTHF, FOOD SOURCES OF FOLATE OR FOLIC ACID AT ALL. That’s a really big deal! Depression is typically characterized by low serotonin states and unfortunately 5-MTHF (or any folate or folic acid). The short explanation for this is that folate, 5-MTHF and folic acid all increase the activity of the transport protein that re-uptakes serotonin into the cell. Essentially this is the opposite of a serotonin reuptake inhibitor (like prozac), it’s a serotonin reuptake promotor – meaning it makes the serotonin you have far less effective because it clears it out more quickly. There will be a whole post on this – I promise!



MTHFR and depression – what is the link here?

MTHFR mutation is becoming kind of the “in” thing to have at the moment and it seems like everyone talks about MTHFR and anxiety, MTHFR and heart disease, MTHFR and depression. The question is, why does a gene for the enzyme that activates folic acid have anything at all to do with those things?  First off, if this sounds like gibberish, then here’s some background reading on MTHFR and on MTHFR and folate. Now – lets see if we can decode the link between MTHFR and depression, because understanding this can hopefully help a lot of people who are struggling start to regain some normal and some happy in their lives.

What is the Link Between MTHFR and Depression?

At the simplest most basic level, your body needs methylated folate (which is what you don’t make very well if you have the MTHFR mutation) in order to manufacture the neurotransmitters serotonin, dopamine, epinephrine and norepinephrine and also the neurohormone melatonin (which helps with sleep among other things). The methylated folate isn’t used directly for these neurotransmitters, but it helps to make something called BH4, or tetrahydrobiopterin if you want to be technical about it. BH4 is then used to help the neurotransmitters building blocks (which are amino acids) to be converted to the active neurotransmitters that your body uses for brain cell signaling.

This is the link between MTHFR and depression, in not so plain english. Great diagram from Dr. Rostenberg, in this post which goes into the subject in more detail. Dr. R was kind enough to give me permission to use this! http://www.beyondmthfr.com/mthfr-depression-folate-bh4-connection/

This is the link between MTHFR and depression, in not so plain english. Great diagram from Dr. Rostenberg, in this post which goes into the subject in more detail. Dr. R was kind enough to give me permission to use this! http://www.beyondmthfr.com/mthfr-depression-folate-bh4-connection/




Um… Still Not Following.

Right – so I honestly don’t think it is hugely beneficial when you’re trying to fix MTHFR  issues in yourself to actually dive too deep into the biochemistry of what is happening because it gets overwhelming really quickly.  Suffice to say that your body has trouble making neurotransmitters if it can’t make BH4 because there just isn’t enough methylfolate. When your body has trouble making neurotransmitters, then you can start to see symptoms including these.

Symptoms of Low Serotonin (Think Negativity and Anxiety):

  • Negative thinking – Pessimistic, cynical or distrusting thoughts.
  • Craving for sweets and starches – Bring on the bread. With a side of fries. These foods temporarily boost serotonin levels in the brain, so you might reach for these more frequently
  • Sleep trouble – You need to make serotonin before you make melatonin (your primary sleep hormone) so this can be a big issue.
  • Low self esteem – Serotonin is one of the chemicals that helps you to feel good about you. Without it, you might feel socially anxious, inferior, or incapable.
  • Anxiety – worry, apprehension, obsessive thoughts and panic attacks are all more likely when your serotonin is low.
  • Aggression – Violence, aggression and suicidal thoughts or actions (violence against yourself) are all symptoms of low serotonin.
  • Impulsive behaviour – Low serotonin can reduce your ability to control impulses.

Symptoms of Low Dopamine (Think No Motivation and No Reward):

  • Lack of Motivation – No real “reason” to do things that matters to you. This also shows up in difficulty getting going in the morning and outright fatigue.
  • Joylessness – Dopamine helps you to actually feel the positive effects of enjoyable things. Without it, everything is a little blah. You have a hard time experiencing pleasure.
  • Memory Loss – Forgetfulness, lack of focus and outright memory loss.

Symptoms of Low Epinephrine and Norepinephrine In the Brain (Think Get Up and Go Got Up and Went)

  • Mentally Worn Out – Mental energy is lacking. All mental effort feels like far too much.
  • Inattention – Can’t really focus on anything.
  • Lack of Excitement – Yeah. Another day in paradise.

The short version of all of this is that without MTHFR you have trouble methylating folate. Without methylated folate, your body lacks Bh4. Without enough BH4, you have low levels of these neurotransmitters and with low levels of these neurotransmitters, everything feels pretty yucky. Like sad, apathetic, anxious, joyless yucky. Is there hope? Hell yes! This isn’t the post for it, but here’s some info about finding the right dose of methylfolate for you, and here’s one about foods that are high in natural sources of folate. It’s a great place to start. Even if you have depression but haven’t confirmed that you have a MTHFR mutation this can be a really great place to start.