S2E27: What is Really Going On With MTHFR Basic State?

Basic state is something that we’ve talked about before, but I want to dive a little bit deeper into why I feel it’s important when other fantastic practitioners, like Dr. Ben Lynch, aren’t really into it. Honestly, there is no right answer here.  So let’s look a little more closely.

The idea of over and under-methylators came originally from the research of Dr. Walsh from the Walsh Research Institute.The main thrust of his research was that mental and emotional disorders often stem from an imbalance or deficiency of nutrients in the brain. 

This research was not based on genetics and had nothing whatsoever to do with the MTHFR polymorphism, or any polymorphisms in the histamine pathway. It was based on Dr. Walsh’s clinical observations over years of working with vast numbers of patients. The terms “overmethylator” and “undermethylator” were his own and based on what he theorized was happening. The names, in my opinion, are a bit misleading because we don’t actually know what is happening with the genetics or if the DNA is really overmethylated or undermethylated. Hopefully, that research will happen eventually, but it certainly hasn’t happened yet.

The reason I like using basic states as a guidepost, is because it’s an easy way, especially in the beginning of your MTHFR journey, to guess how you might respond to certain supplements and drugs for mental health.  This can be hugely helpful because we all have a tendency to dive into the deep end with this, and believe me – taking a big dose of methylfolate if your body isn’t ready for it can scare you off of taking methylfolate for a very long time. 

Also, since the basic state is based on observable personality traits, allergies, and measurable signs and symptoms, we’re not looking at just one gene. We’re looking at how the totality of a person’s genes plays out in real life, because how they look on paper isn’t always how they act and how they act is what really matters at the end of the day.

Also, this is something that can be determined without any genetic testing, without any specialized help from practitioners and without the need for any fancy interventions at all. That makes it extremely valuable because for every one  person who thinks they have an MTHFR polymorphism who is working with a knowledgeable practitioner, there is another hundred who are doing this on their own.

For that, basic state is invaluable. Also, I love the fact that it’s based on what is called phenotype, or genetic expression, not genotype, or genes as they’re written. What that means, is that elements like personality traits or high or low histamine, represent the way all of your genes come together to express, which is by far more valuable information clinically than the actual gene polymorphisms themselves. 

There are so many genes involved in each pathway – when you look at actual gene expression, or phenotype, you’re seeing the way all the genes come together, which is more relevant than just the status of one gene or another. Also, all of your genes express or don’t express depending on a variety of factors including lifestyle, nutritional status, other health factors and even your mother’s health status while you were in utero. It’s far more complicated than just this or that gene, but looking at who you are as a person and how your personality expresses is actually a great way to sum up this information.

Knowing your basic state can give you some well informed starting places in terms of how you will respond to supplements, pharmaceutical drugs, and even the types of doses you might expect to be optimal. It isn’t 100% accurate, but it gives you a better idea of starting places than you would otherwise have. Still always start low and go slow, but knowing your basic state can speed up the process of discovery. 

The MTHFR Basic State Mirror Image

When you’re trying to determine your own basic state, it’s most helpful to think of them as flip-sides of the same coin with opposite traits on either side.  Your basic state will come down to how many traits you have from each side.

For instance, the traits of overachievement and perfectionism show a subtle but important difference. Both under and over-methylators express these traits, but undermethylators tend to be perfectionistic and overachieve in all areas, where overmethylators hyperfocus on the areas that are important to them and let the rest slide.

There is a very important difference in allergic response as well. High histamine type allergies and sensitivities are like classic hay-fever, where you open a window and the pollen instantly makes your eyes stream and starts the sneezing.  That is an undermethylation, high-histamine type reaction. Overmethylators, on the other hand, show more chronic allergies and sensitivities – the low-grade headache, neck tension, entire season with a blocked nose that doesn’t particularly change whether you’re indoors or out. That is a low-histamine sensitivity pattern. Also, overmethylators tend more toward chemical and food sensitivities, where undermethylators tend more toward histamine intolerance in foods.

UndermethylatorTraitOvermethylator
High, for everythingAchievement and DriveHigh for the thing that matters to them, low for other things
Typically follows rules and social norms wellRules and guidanceFollows rules that make sense to them, disregards others. Follows the beat of their own drum.
Typically pushes for achievement in everything they doAchievementPushes for achievement in the things that matter to them, but not interested in other things
High histamine and seasonal allergiesHistamineLow or normal histamine with chronic allergies/sensitivities
Typically lowerPain ToleranceTypically higher
Often intolerant to histamine in foods, but less often to foods themselves.Food reactionsTypically has sensitivities to specific foods and chemicals
High fluidity (saliva, tears, etc…)FluidityLow fluidity (saliva, tears, etc…)
The MTHFR Basic State Mirror Image

At the end of the day, trying to decipher the big picture by looking at each particular gene SNP can lead to a really messy situation in which you can end up taking supplements that look good on paper, but aren’t actually addressing the issues you have in real life.  This is far less likely to happen if you’re working with a good practitioner, but sadly I’ve seen some practitioners fall victim to this mentality as well. Even worse, you can end up taking one supplement for each gene SNP and getting completely overwhelmed by a cumbersome protocol that costs a lot of money and time, but doesn’t get you anywhere.

If you’re looking for a MTHFR basic state refresher, you can follow this link to learn more about the idea in general. Here’s a link to dive deeper into the undermethylator picture and here’s one for overmethylators.

Thank you so much for listening today, and if you haven’t done so already, check out the show notes at tohealthwiththat.com. There are resources, downloads, links to research, and best of all an email list where you can sign up to be sure you’re the first to hear about exciting new courses, free resources, and other great things.

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S2E5: Patience with MTHFR

I’m pretty sure that this is the most frustrating part of the whole MTHFR shebang. Not the crazy symptoms, the issues if we take too much methylfolate, the dietary changes, or the problems we have from MTHFR in the first place, but the tooth-grindingly frustrating requirement for patience.

I am not a patient person. My nature is to rush headlong into everything, and consequences be damned. It’s actually a family trait – my grandfather once rear-ended a moving vehicle the highway because they weren’t going fast enough. Of course, both vehicles were land-yachts, as was the norm at the time, so the worst that came of it was a very startled driver in the other car. My mother physically can’t stand still, and if there are more than two people standing in one place then it’s a line, and she’s not interested.

My family is not good at resting on our literal or proverbial laurels.

Interestingly, this is a trait shared with many MTHFR folks, which always makes me question whether the universe actually is some giant cosmic joke – a huge “gotcha!” situation in which every human is required to muscle through the tasks that are the hardest for them as individuals to tolerate. It certainly seems to be the case with MTHFR, because so many of us like to push forward and push through, and we are generally capable of doing so.

In general, MTHFR folks fall into two categories, or basic states. Those are overmethylators and undermethylators. If you don’t remember what I’m talking about, this is your MTHFR basic state and represents the two halves of the MTHFR coin. Both faces of this coin have many commonalities, but the differences come down to whether your body likely overmethylates your DNA or undermethylates it. Another way to look at the whole thing is by looking at your histamine levels. Both sides of this coin react to lots of things in the outside world, but undermethylators react in a high histamine way – picture sneezing, hives, watery nose, itchy eyes. Overmethylators react in a low histamine way – think constantly blocked nose, allergy headaches or muscle pains, chemical sensitivites. This idea was proposed and researched by Dr. Wash of the Walsh Research Institute. To brush up on the basics, follow this link to S1E16 on MTHFR basic states.

Overmethylators

Overmethylating MTHFR folks are known to push themselves through all manner of agony for their passion project of the moment. Typically, it is some kind of activism, some sort of making the world better, something that helps others, or an art form they are offering to the world. It could be a skill taken to the level of art or anything these amazing MTHFR folks choose to push forward. If you want more detail on overmethylation, check S1E31 which did a deep dive into the state of overmethylators.

Overmethylators, you’ll recall, tend to excel at the things they’re interested in and the rest of it can go hang. These are often the brilliant children whose parents don’t understand how they can know and understand every map, level, move, and function in a complex video game, but won’t learn to read. These MTHFR folks aren’t concerned with doing well at everything, but they will go above and beyond at the things that interest them. These are the folks who forget to eat, sleep, or do anything while they’re in the flow of their work or interest. As a whole, patience isn’t the watchword here.

Undermethylators

Sadly, patience isn’t something these people possess in great quantity either. Undermethylators are our perfectionists and overachievers and they make up about 45% of the population. There are also people who are methylation neutral, but people with MTHFR mutation tend not to be. Undermethylators are the people who will push themselves until they collapse to be the best at whatever it is that they do. They’re the prima ballerinas, the professional athletes, the CEOs, and the people who generally push until they are the best that they can be at everything they do. They are typically perfectionists and expect themselves to excel at everything. If you want a refresher on undermethylators, it can be found in S1E32.

As you can see – both of these groups push forward no matter what, and that typically doesn’t involve patience. But in this game, patience is the essence of what is needed.

Why So Much Patience?

Patience is necessary with MTHFR simply because we are dealing with a pathway that is inherently compromised and that pathway is responsible for many things, but utterly dependent on a couple of nutrients. This creates a situation in which there is a mountain of pressure in all of those un-done responsibilities on a very narrow platform of nutrients. In short, this is a situation that can get messy in a heartbeat.

I think far less patience would be required if we all started managing our methylation at birth. Babies would be raised with all of the good active methylfolate that they need and the other B vitamins would be available too so that there wasn’t a chance for this slightly compromised system to create a backlog of unfinished business.

Most of us are not raised like that. Most of us have a good 20, 40, even 60 years of backlog built up before we actually figure out that there is even an issue with MTHFR, and so we need patience. Changes must be made slowly for a few reasons.

  1. If you make too many changes at once then you can’t tell what is doing what. So if you have any kind of reaction, bad or good, you don’t know what to link it to. So confusing.
  2. If you make a great change, like adding 5-LMTHF, but add too much too quickly, you can get into super scary too-high-a-dose symptoms, which mostly feels like you could peel the paint off the walls just by looking at them hard enough. It’s not fun and it usually makes people give up methylfolate forever or at least for a few years until they get brave enough to try again.
  3. If you make a conservative change – like adding a small dose of 5-LMTHF, but then don’t wait for your body to settle in and be ready for the next step, then you get into massive symptom territory again.

Essentially, the MTHFR journey is like walking a very long boardwalk through a crocodile-infested swamp. You want to stay on the path and not veer off into the muck. There, be dragons.

I know that everyone listening wants the next step. Right now. Do not pass go, do not collect $200. I know that. But the next step is actually waiting to see how you feel without folic acid in your diet and with the addition of food sources of natural folate. It’s symptom tracking.

Some of you won’t notice too much. That’s ok.

Some will notice an improvement, and that’s a great sign that you’ll be able to take the next steps post-haste. This tends to be overmethylators, who typically tolerate 5-LMTHF reasonably well.

A few, will notice that without the folic acid things were looking brighter but adding in the foods high in folate doesn’t work for them. Or, it makes them worse. In fact, some of you might have already known that none of the high-folate foods I’ve mentioned work for you at all. This could be an indication that you’re not going to tolerate folate – and that’s ok. Think of this as an early warning system. We will still eventually try to add in a tiny dose of 5-LMTHF, but the red flags are already up – we know in this scenario to take it extra slow and to watch for bad reactions.

Thanks for listening and just as a heads up – I am launching a patreon page because I love making this podcast and I want there to be as much free information out there for MTHFR folks as there can be. If you feel like you’re getting some help with this information, I would be delighted if you could contribute a bit there. My page isn’t live yet, but it will be by next week, so stay tuned.

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Overmethylator or Undermethylator… What Is Your Basic State?

Different Opinions of Methylation

There are several different versions of this conversation floating out there on the web, and this is a point that matters very much in terms of finding the right MTHFR solutions for you.

Typically, people with MTHFR mutations have one of three basic states – overmethylation, undermethylation, and neutral methylation. Knowing your basic state can help you to track your progress on your MTHFR journey, and know when you’re headed in the right direction.

Which way do you lean on the methylation spectrum?

Undermethylation, according to the Walsch Research Institute, is the most common human state at around 45% of the population. Neutral methylation makes up another 40% of the population and Overmethylation constitutes the remaining 15% of the population, solidly holding the black-sheep positions in most families. Most people will have symptoms and personality traits on both sides of the spectrum, but you might notice more of a trend in one direction or the other.

Overmethylation (15%)Undermethylation (45%)
Marches to the beat of their own drumTypically  mentally healthy, but overly driven
Depression – mixed neurotransmitter issuesDepression (low serotonin)
Paranoia or anxietyPerfectionism (this can also look like anxiety)
Head and neck painObsessive or compulsive tendencies
Highly creative and often gifted artists or musiciansRitualistic behavior
Low motivation or hyper-motivated but only in what is interesting to them (not globally).High motivation
Self-mutilation or heavy on the tattoos, piercings, and other body enhancementsAddictive personality
Non-competitiveCompetitive
Food or chemical sensitivitiesSeasonal/inhalant allergies
Sleep often disorderedStrong-willed
Diminished tears or saliva (low fluidity)Excessive tears or saliva (high fluidity)
Highly empathic and sensitiveFrequent headaches
Pacing or constant movementPoor concentration/mental endurance
High pain thresholdLow tolerance for pain
Ruminating – mind has a hard time shutting offSelf-motivated
Tend toward more hair (head and body)Tend toward sparser hair (head and body)
Often reacts badly to SSRI medications – better with benzodiazepinesOften good reaction to SSRI medications
Often reacts badly to antihistaminesOften good reaction to antihistamines
Often reacts badly to estrogen therapy (or birth control pills)Can have delusions or thought disorders
Passionate and self-sacrificingHistory of high accomplishment
Do you lean toward one of these?

This is One Place Where I Don’t Agree With Ben Lynch

Some people, with the notable MTHFR expert Ben Lynch being one of them (if I’m interpreting his work correctly – feel free to correct me if I’m wrong, Ben!) seem to use the term “overmethylated” as synonymous with either “over-supplemented” or “pushing methylation pathways too hard.” (I”m getting this idea from this post on MTHFR.net).

Others, like myself and Dr. Walsh of the Walsh Research Institute, use the term more to describe a person’s basic natural tendency based on their genes and also the ways their genes are influenced by the environment (epigenetics). Of course someone in this view who is overmethylated can also over supplement, but their basic state, personality traits, and natural tendencies are still those of an overmethylator. Truly, how often do you see the overachiever (undermethylator) of the family turn into the black sheep (overmethylator) because of a supplement, and then stop it and turn back into the overachiever?

Can you tell your basic state just by comparing yourself to these two pictures?

Using Your Basic State As A Guide

Understanding and using both your basic state and your symptom profile can help you to understand when you’re moving toward health and more balance, or in the opposite direction toward imbalance and disease. I like to think of it as pushing my own pathology.

This is a great way to help you understand when you’re on track because some of these symptoms are easy to track and might change before more serious physical issues shift. For example, it’s easy to tell if you’re having a good or bad day for ruminating, when your concentration is clearer or when you’re not quite as perfectionist as you usually are. These are easy for most people to rate on a symptom tracker, but might not be things they would have put onto the symptom tracker if they didn’t know their basic state. More long-term issues like inflammation or blood pressure respond more slowly. This can be a very immediate tool to help you assess your symptoms today.

Whether you’re an overmethylator or an undermethylator, balancing your basic state can only help.

So, Will I Suddenly Have A Different Personality?

Absolutely not. The passionate artist or activist is still going to be a passionate artist or activist, but they will be more balanced and more able to keep themselves healthy while being a passionate activist. Likewise, the highly competitive overachiever will still be a highly competitive overachiever, but they’ll take better care of themselves, take breaks for sleep, not push themselves so far into damage in order to overachieve. Balancing your methylation doesn’t change who you are. It unlocks the best of you.

Thanks so much for tuning in and if you can, give me a shout and let me know if you’re an overmethylator, undermethylator, or a neutral methylator.

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