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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Supplements for Depression with MTHFR

MTHFR and depression are intimately linked. We’ve spoken about this before, and if you want to brush up, take a look at Season 1 Episode 8 where we explored the link between the MTHFR mutation and neurotransmitter formation via the BH4 pathway. The quick and dirty version is that when methylation isn’t working optimally, then the pathway that makes many of your major neurotransmitters, including serotonin, melatonin, dopamine, epinephrine, and norepinephrine gets stalled out too.

Season 1 Episode 33 was also all about MTHFR and depression, specifically the entirely fixable causes of depression that your doctor will typically overlook. This whole episode was about steps you can take at home to manage depression. Balancing your methylation is obviously a cornerstone, but there are so many other factors involved that are entirely in your hands.

Another great one to review is Season 1 Episode 34, where we talked about the component of depression that is quite simply a mental bad habit. The part that feels like falling into a rut mentally where your brain travels over the same tracks, the same complaints, the same problems without questioning them or without breaking those patterns. Also, Season 1 Episode 35 in which we talk about some great techniques for breaking those bad habits.

The part of depression we haven’t talked about yet is the supplement part and this is something that people ask me about all the time. At the end of the day, sometimes we really do need a pill to take the edge off while we’re making these other changes. Often, the supplement helps us to have the mental and emotional energy TO make other changes. So let’s talk about a few good options that are typically pretty safe for MTHFR folks and typically well-tolerated.

Some Amazing Depression Supplements We Won’t Be Talking About

There are some great supplements for depression that we won’t talk about today, mostly because we’ve talked about them before at great length. One of the best natural treatments for depression is, of course, balancing methylation using a good folate source or SAMe and a good B12 source. Since those are things we talk about pretty much every week, I’m going to assume you’ve got those covered. For most of my clients, balancing methylation – whether it’s through 5-LMTHF, folinic acid, food sources of natural folate, or SAM-e – is the cornerstone of their depression relief. That doesn’t mean it’s the only thing they need to do, but it’s certainly the foundation.

Another effective supplement for depression that we’ve talked about before is St. John’s Wort. We dove into that one at some length in Season 1 Episode 46 on the link between MTHFR and serotonin. Also, omega-3 fatty acids and fish oils are extremely well studied for depression and we’ve also talked about those at great length because they boost the effectiveness of B vitamins in MTHFR mutation (Season 1, Episode 42). Just remember that if you’re using fish oils for depression you may need a higher dose than the one listed on the bottle.

Saffron For Depression

Saffron is best known as a spice, adding brilliant yellow color and subtle flavor to Middle Eastern food and haute cuisine. Like most other highly-colored spices it’s absolutely packed with antioxidants, carotenoids, and biologically active compounds. In research and clinical practice, saffron shows major benefits for those with depression and it is thought that this could be through some serotonin-boosting mechanism, possibly similar to SSRI medications in which the saffron keeps serotonin in the synapse longer, basically making the same amount of serotonin do twice the work.

In fact, when compared to the actions of SSRI medications, saffron was found to be just as effective for major depressive disorder as these commonly prescribed pharmaceuticals.

Given that this is thought to directly affect serotonin levels, it is best to talk with your doctor before starting saffron if you are already taking an antidepressant medication because there may be an interaction between them.

Saffron is typically dosed around 30 mg per day in research studies.

NAC for Depression

NAC or N-acetyl cysteine is something that we have talked about before as a precursor to glutathione, which is one of your body’s key antioxidants. It is actually precisely because of this function that it is so useful for depression. People with depression are more likely to have higher levels of oxidative stress, inflammation, and inflammatory cytokines like C-reactive protein, tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6). By helping to moderate the inflammation, NAC actually eases symptoms of depression as well.

It is thought that NAC helps to regulate glutamine and dopamine levels in the brain and demonstrates a great ability to both cross the blood-brain barrier and also to increase levels of glutathione within the brain and central nervous system. NAC also shows promise for use with addiction and substance abuse issues.

NAC is actually an amino acid and so it is best taken on an empty stomach. If it is taken with food, then it competes with other amino acids for absorption. The doses typically used for depression are between 2 and 2.4 g/day. This can be divided into two or three doses depending on what is easiest for you to manage.

Rhodiola for Depression

Rhodiola is well known as a supplement for helping to get core energy back in situations of adrenal fatigue or exhaustion. This is because of its action as an adaptogen, and that adaptogenic ability is also thought to be the reason it helps with depression.

Studies have linked hypothalamic-pituitary-adrenal axis dysregulation (or HPA axis dysregulation for less of a mouth full), with depression. HPA axis dysregulation is exactly what is happening in clinical cases of adrenal fatigue or exhaustion. It describes a state of over-reactivity and subsequent burn-out of this vital neuro-endocrine system.

In a study that compared the effectiveness of Rhodiola to the common antidepressant Sertraline, the Rhodiola was shown to be effective, but not quite as effective as the antidepressant, but also far better tolerated with fewer side effects.

The typical dose of Rhodiola for depression is around 340 mg per day. There are other adaptogenic herbs as well, all of which may have similar benefits for depression. These include licorice root, ginseng, American ginseng, schizandra, and ashwagandha.

Thank you so much for listening, and if you’re interested in a 6-weeks to health with MTHFR course, make sure to sign up for the mailing list at tohealthwiththat.com and keep listening to the podcast for more info.

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Supplements For Anxiety With MTHFR

We’ve talked about how MTHFR and Anxiety are linked a couple of times and had an interview with anxiety expert Jennifer Bronsnick, but all of that still doesn’t answer one of the biggest questions about anxiety that I get, which is, “What can I take to help me fix it?”

Good question. Obviously, everyone responds differently to different supplements, just like they do with medications, but here are a few of my favorites with some perspective about how they interact with MTHFR. I’m hoping it goes without saying, but balancing your methylation should always be the first step to dealing with anxiety. The rest of these are to clean up anything that is left.

GABA

GABA is, in my opinion, a highly underrated supplement. It is an inhibitory neurotransmitter, meaning it decreases the likelihood that the neuron will fire or send a signal. In the overactive brain of someone with anxiety, this is precisely what we want. It is also crucial to healthy brain functioning, with an estimated 60 – 75% of all neurons being GABAergic (or responsive to GABA.)

There has been a long-standing debate in the research world whether or not GABA that you take by mouth can possibly cross the blood-brain barrier. It is certainly well absorbed and blood levels rise sharply within thirty minutes of taking it, but it is much harder to demonstrate brain levels in a study. Research evidence and theorizing exist on both sides of the fence, but due to its potent clinical effects, I tend to think it either does cross the BBB or it takes action on something else which has a calming effect on the central nervous system and that is just as good.

GABA is probably most known as a sleep aid, helping to calm restless minds into healthy sleep. For anxiety, however, it reduces your feeling of actual anxiety and tension, but also helps to reduce cortisol levels, increase parasympathetic nervous system activity as measured through the vagus nerve (which means your nervous system is trending more toward relaxation than stimulation). The doses used in research tend to be between 30 – 100 mg. There is a great systematic review article about GABA and its effects on anxiety from Frontiers in Neuroscience here.

GABA is the type of supplement that I feel sneaks up on anxiety. What I mean by that is taking a dose regularly that is just below the dose that would make you sleepy (this might take some trial and error) isn’t necessarily going to change your life in that first week, but it does help to get your body into a rhythm of functioning without as much hypervigilance. I love this because it takes the edge off so that you can actually work on mindfulness or breaking mental bad habits in a more protected mental space – like the GABA makes it easier to see the things your mind is doing that it doesn’t need to be doing.

As an aside, GABA also shows remarkable clinical promise for Type I Diabetes, which is insulin-dependent. In much larger doses than those taken for anxiety, GABA helps to boost insulin response in fasting and non-fasting conditions and may help to both protect and restore pancreatic beta cells. While this has very little to do with anxiety in the way we tend to think of it, there is a link between anxiety and blood sugar.

MTHFR and GABA

There is only one relevant study pertaining to MTHFR and GABA levels. This study shows mice with MTHFR polymorphisms to have altered levels of many neurotransmitters, including GABA, in different brain segments relative to wild-type mice. This study showed that mice who were heterozygous for an MTHFR SNP showed altered levels of both GABA, which is inhibitory, and glutamate, which is excitatory, in the amygdala, cerebellum, hypocampus, and thalamus.

Passionflower (Passiflora Incarnata)

Outside of having one of my favorite names in all of herbal medicine, passionflower is remarkable as a calming and soothing agent for anxiety. It can be used for short-term anxiety, such as to help patients remain calm before dental or surgical procedures or long-term for such neuropsychiatric conditions as generalized anxiety disorder and post-traumatic stress disorder. In both cases, passionflower shows remarkable benefits.

A comparison study between liquid passionflower extract and the pharmaceutical drug oxazepam, which is a benzodiazepine, showed equivalent clinical effectiveness over a period of 28 days.

Passionflower has also been used to help people who are addicted to opiates to successfully withdraw. Studies showing passionflower as an addition to clonidine, which is the standard of care, demonstrate better handling of mental symptoms in the clonidine plus passionflower group than the clonidine alone.

Passionflower can be taken as a tea, a liquid extract, or as a capsule or tablet. As with all herbal medicines, quality matters and it’s important to find products that follow the highest standards of manufacture and testing.

While passionflower hasn’t been specifically studied for use in folks with MTHFR mutations, it works well clinically in a wide range of people, and I’ve seen great results in my own clients, the majority of whom have MTHFR polymorphisms. Also, it’s pretty easy to tolerate and side effects are not common.

Adaptogenic Herbs For Anxiety

Adaptogens are herbs that help the human body resist stressors of all kinds. They quite literally help us adapt to all manner of situations with grace and strength, both literal and metaphorical. The most well-known adaptogens are herbs like ginseng, ashwagandha, and licorice which might just as well come with a sub-heading that says “Strong Like Bull.”

While there is, sadly, no research specific to MTHFR and adaptogens, there is a literal boatload of research on adaptogens and anxiety. Ashwagandha, for instance, has been shown to reduce both the feeling of anxiety and also cortisol levels after 60 days in adults with a history of chronic stress.

In general, the effects of adaptogens on cortisol levels and conditions associated with excessive cortisol, including anxiety, fatigue, abdominal obesity, and metabolic syndrome, are extremely well known. These are wonderful therapies for the management of long-term stress and anxiety disorders, although they should be used with practitioner supervision and guidance.

Licorice, for instance, is one of my favorite herbs of all time, but it is known to elevate blood pressures and so is perfect for skinny, high-strung, anxious women like myself, but not a good option for someone who struggles with blood pressure or cardiac issues.

There are, of course, hundreds of other supplements for anxiety but these are three of my go-to staples. Don’t forget to sign up for the mailing list, or join our MTHFR community here.

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S2E20: MTHFR and Anxiety – An Interview with Jennifer Bronsnick

This week on the podcast we’re trying something new. An interview with an anxiety expert who has also gone through her own recovery process with anxiety. The interview was clipped for the podcast episode but you can watch the full thing, on zoom, here.

MTHFR and Anxiety – an Interview with Jennifer Bronsnick.

Jennifer Bronsnick’s suggestions for Anxiety

Jennifer mentions a few tools that have been helpful for her. Here they are!

  • Eliminating alcohol
  • Cutting down or eliminating refined carbs like white flour and sugar
  • HeartMath – for more info about this, click here.
  • Existential Kink – the book by Carolyn Elliott.
  • Getting quiet to actually hear what your body might be trying to say.

Let me know what you think of the interview format – I can do more of this, or not. Just depending on you.

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S2E19: MTHFR and Anxiety

MTHFR and anxiety are intimately linked, mostly, we presume, because your body needs folate to make serotonin, dopamine, epinephrine, and norepinephrine. Those are most of the major neurotransmitters that affect mood and mood disorders including anxiety and depression.

More specifically, a folate molecule is needed to convert BH2 to BH4, and BH4 is needed to convert the amino acid precursor tryptophan into serotonin and tyrosine into dopamine, norepinephrine, or epinephrine. We did a post about it here.

Because of this link, working on optimizing your methylation can have a huge impact on anxiety and depression, but it isn’t the only thing you can do. Of course there are pharmaceuticals for anxiety and I’m not really going to cover those because those will probably be your doctor’s first go-to solution. And that’s fine, but there are other things as well. We’ve already talked about anxiety as a mental bad habit, and also about breaking mental bad habits. So today, let’s talk about steps you can take in your own real life to reduce anxiety.

Eat Regular Meals

This kind of sounds like a soft-ball. Like it couldn’t possibly make a difference to anybody’s anxiety level because it’s just too simple. In reality, keeping your blood sugars balanced and stable can cause a huge drop in anxiety levels, and here is why.

When your blood sugars drop, either from a skipped meal or after a sugar rush and the inevitable sugar crash that follows, your body has a low-sugar stress reaction. Sugar is absolutely vital to the functioning of your brain and so your blood has a tightly regulated amount. If that amount drops, your body literally goes into panic mode, activates your HPA, which is your hypothalamic-pituitary-adrenal axis, and pumps out stress hormones to bring your sugar levels back up.

Skipping meals is incredibly stressful for your body – and that translates to actual stress hormones that affect your level of anxiety. Keeping your blood sugars balanced through the day is far more important than you realize, and if anxiety is an issue for you, then it’s important to back some of the sugar out of your diet and make sure you eat regularly.

I know plenty of people who run on adrenalin and skip meals regularly because they’re too busy, there’s no time when the kids are running around, etc… but making time for this simple self-care can have a huge impact on how stressed you feel and also on the long-term effects of stress like sleep quality, weight gain, belly weight, and fatigue. Interestingly, blood sugar fluctuations and their corresponding changes in insulin levels are also highly linked to brain fog.

Clean Out Your Medicine Cabinet

Oddly a number of medications are known to increase anxiety. Some of those are because they have a negative effect on folate status, like birth control pills or methotrexate. Some are because they cause a caffeine-like reaction (or actually contain caffeine). These include cough and congestion formulas, many pain pills, and cold and flu medications. Also, medications for weight loss are well known for causing anxiety. Also if your dose of thyroid medication is either too low or too high it can lead to anxiety.

Decrease Your Caffeine

First, a disclaimer. I am a *huge* fan of coffee and will never, ever, ask you to stop drinking it. Having said that, different people have different levels of sensitivity to caffeine and also, women at different points in their cycle have different sensitivities to caffeine. It can help to experiment with your caffeine intake to see what works best for you, but keep a symptom tracker for a few months and try different caffeine levels – you might be surprised. In truth, any human with more caffeine than their body can easily process, is going to experience more anxiety, more edginess, and more irritability. That is just biology, so it can be a good idea to check in with your body every now and then and see if the amount you’re getting is ok for you.

Many medications contribute to anxiety, especially those like methotrexate or birth control pills that decrease folate levels.

Exercise, Yoga, and Meditation

These are all well-known moderators of anxiety, so I won’t belabor the point, but there are a few tips.

  • According to a study published in Psychiatry Research, higher intensity exercise like jogging or fast walking shows better results for reducing anxiety than gentle stretching.
  • Yoga shows better effects for anxiety than stretching or resistance training in Parkinson’s disease, but that effect may translate out to the general population as well.
  • Mindfulness meditation (as opposed to other forms) has been well documented to reduce anxiety symptoms.

There are, also, a number of supplements that are helpful for anxiety as well, but we’ll cover that in a separate post.

Thank you so much for listening today and please sign up for the mailing list at tohealthwiththat.com – we’ve got some great things coming this year and I want you to be the first to know.

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S2E17: Happy Holidays and How To Make A New Years Resolution You Will Actually Keep.

First and foremost I want to say happy holidays this week. Spend time with loved ones if you can, and if you aren’t able to be with the people who matter to you, then make sure they know they matter in some way or another. This is the season when we all need to give and receive as much love and care as possible.

The holidays can be a hard time for a lot of people. If you’re struggling this season as so many people are, please reach out to someone. It could be a friend, a practitioner, family, a shelter, or hotline. Ask for help if you need it – you will be surprised at how much help is available.

This year is coming to a close and that brings with it a measure of self reflection and the almost inevitable decision to make some changes. For many of us those changes will come in the form of a New Years Resolution, and this year I’m proposing something a little bit different. Here’s why.

Saying “I love you” to yourself is surprisingly powerful. It only takes a second – try it right now.

2021 has been a tough year. Partly, because it followed 2020, which was also a tough year. Never-ending the global pandemic, many of us have faced some pretty extreme changes to the way we chose to live, the way we socialize, the way we work, the work we do, and our perceived level of freedom. I want to take a minute to acknowledge how much stress we as a collective are actually under and to honor that.

With MTHFR, it is wise to buffer ourselves from stressors like this one, and for many of us, this pandemic has worsened anxiety, increased depression, or deepened or reactivated addictions. Not only that, there is evidence that Covid affects people with MTHFR who have high levels of homocysteine more strongly than it does other folks. I want you to take just a second, take a deep breath, and say something profound. I want you to look in the mirror, right into your own eyes, and say three simple words. “I love you.”

For some of you, that will be kind of awkward or odd, for some it will trigger a smile and for some it will trigger tears. No matter what happens, this is a powerful thing you can do for yourself in only a second and it matters this year.

Now, back to the issue of New Years Resolutions.

I honestly feel that precisely zero people need more stress or striving right now. What we need is more joy, so I’m proposing a different kind of resolution this year – one you might actually keep beyond January 3rd. Here’s how to do it.

  1. Write a list of things that make you happy that you don’t take the time to do right now.  It could be big things (like travel or vacation or family camping trips) or little things (sketching, hiking, or having fresh flowers in the house). Think of at least 20 things.
  2. Take out the ones that are impossible  for some reason (costs too much, borders are closed, have to stay close to home to take care of elderly parents, etc..)  
  3. Make sure there are at least ten good things on your list and if there aren’t, repeat steps one and two until you’ve got ten or more
  4. Make your resolution, just like the big bold one below.

In 2022 I will do one wonderful thing from my happy list every week.

– Love, me.

How’s that for a resolution you can keep?!?

We all need a little more happy and a little more ease right now and putting pressure on yourself, guilting yourself, or being hard on yourself, or setting yourself up for failure isn’t going to help anybody – especially not you.

This year, make a resolution that will make your life better.

Happy New Year, Everybody! Love, Amy.

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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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How Do You Know When Your Methylation is Balanced With MTHFR?

It’s great to talk about “balancing your methylation” and finding your right folate dose, but how do you know when you’re actually there? This question matters a lot because I’ve seen so many clients who are on a constant upward trend with their methylfolate dose – always pushing to take more simply because they can tolerate it.

The point is, do you need it? Is it helping you? This isn’t a contest in which the person who takes the most methylfolate wins a prize, this is about listening to your body and finding balance – balance meaning not too much and not too little. This goes for MTHFR folks, but also people without an MTHFR polymorphism, because you don’t have to have MTHFR to have imbalanced methylation.

So where is this elusive magical place in which balance is reached? It may not be nearly as elusive, nor as magical as you’re thinking.

Does Balanced Methylation Mean All My Symptoms Are Gone?

Goodness, I wish it did. It usually means most symptoms are better, and some of them are gone, but all of your symptoms being gone is not actually realistic. We’re all human and human bodies are built differently for lots of reasons. One of those is MTHFR, but each human has hundreds of polymorphisms along with a whole life history of pathogens, traumas, nutritional factors, lifestyles, and varying degrees of self-care. Balancing methylation can’t compensate for all of that, it just takes a big chunk out of the bottom.

Having said that, the process of balancing your methylation usually helps people tremendously – decreasing anxiety, softening depression, improving sleep, reducing inflammation, normalizing hormones and generally getting things closer to where they should be.

What Is The Easiest Way To Tell If My Methylation Is Balanced?

There are two great ways. The first is to look at the work you’re doing around methylation. The second is to look at your labs.

Caring For Your Methylation

You know you’re at a place where your methylation is balanced when these things are happening:

  • You understand the signals your body gives you when it needs more support and when you’re taking too much methylation support
  • You respond appropriately to those signals
  • You aren’t hitting major walls coming from detox symptoms or up and down methylation crashes
  • Your symptoms are slowly but surely softening and resolving. THey may not be fully resolved, but you’re on an upward trajectory. Some of this just takes time.
  • Your body’s basic needs are regularly met – you’re getting good nutrition, good sleep, gentle exercise.

I see the same panic-stricken look on many faces when I say this, especially from folks at the beginning of their journey. Don’t worry – this all becomes clear over time and this is a journey that takes time. In good news, the best way for it to all unfold, is softly. This is a lot like pregnancy in that you can’t really rush it – it’s best to just support the process. For everyone who has just muttered something grumpy under their breath, the next section is more concrete. I promise.

Ok – So What About Lab Work?

Basic bloodwork can tell you a lot about what your body is doing at that moment. Values that are most specific to methylation are:

  • Serum Folate
  • Serum B12
  • Serum homocysteine

There are also some tests that are suggested on various MTHFR forums that I am less inclined to use including:

  • Serum MMA
  • RBC Folate
  • Urine MMA
  • Urine FIGLU

We’ll go through the tests I use one by one. The tests I am less inclined to use we’ll cover in a different post.

Serum Folate Test

This is the standard folate testing t and sadly doesn’t differentiate between useful folate that is bioavailable and folic acid or worse, unmetabolized folic acid. So this test will tell us if there is an overt folate deficiency, but not much else. Still, knowing if you have a folate deficiency matters with MTHFR. Levels below 4 mcg/L indicate a folate deficiency, but outside of that, the guidelines are vague. I don’t like to see the numbers creep too high either and >8 mcg/L can also be a red flag for over-supplementation, or for high lingering folic acid and unmetabolized folic acid in the blood.

Serum B12 Test

This test measures levels of B12 in the serum and is reasonably accurate, but has a broad reference range. The reference value is typically 180 – 914 ng/L and anything in there is considered normal. Anything below 180 ng/L is considered to be deficient. Because it is such a broad range, I tend to look at anything even close to 180 ng/L with suspicion. Remember reference ranges give us the average numbers where people begin to experience symptoms, but that doesn’t mean it’s the ideal number for you, so aim for the middle of the range (somewhere between 450 – 650 ng/L). Also, if you test normal but still have symptoms of B12 deficiency, then extra supplementation could be warranted.

Serum Homocysteine Test

We’ve talked a lot about serum homocysteine and there is a normal range and also an optimal range. If you’re outside of normal, then obviously there’s a problem, and for MTHFR folks it’s a good idea to aim for optimal. The normal range is 5 – 15 umol/L with optimal being 6 – 9 umol/L (in my opinion. Follow the link to see my reasoning.) Homocysteine, remember is an inflammatory marker in the blood that is a direct measure of how well you’re methylating methionine and so is the clearest measure of MTHFR function.

Are There Other Tests?

There are other tests, namely serum MMA, urine MMA and urine FIGLU. These tests are less commonly used and deserve a post of their own when we have more time. I find the serum folate, serum B12 and homocysteine to be the most useful of the bunch.

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MTHFR and JoyHacks – Boost Your Happy

Joyfulness is a beautiful and elusive thing. It’s easy and common to get bogged down with the everyday life stuff. The things that need doing, or cleaning, or getting, or disposing of. There are lots of repetitive activities, frustrating waits, stressful rushes. I get that. There is also, in all of these moments, an opportunity to be happier.

We’ve just finished talking about MTHFR and the different neurotransmitters – serotonin, dopamine, norepinephrine, and epinephrine as well as my somewhat offbeat neurotransmitter theory so it seems like a good time for some joyhacks. Small, everyday things you can do to boost your joyfulness long-term.

#Joyhack – a small everyday action, activity, or behavior that will actually boost your joy. Proven by science.

Amy Neuzil from tohealthwiththat.com

Simple Joyhacks with A Big Impact

I am 100% sure you’ve seen a list like this before, but the question is, have you acted on it? I talk to so many people about joyhacks who say they’ve heard of some of these actions but haven’t actually added any of them into their daily routine.

Almost all of these will take 5 minutes or less, with the exception of exercise (shoot for 7 – 10 minutes at least) and meditation (if you can get 10 minutes, you’re great!) These aren’t hard, you just have to remember to do them.

  • Set small goals, and meet them. The simple joy of crossing something off a list actually boosts your dopamine. It also boosts your self-confidence because every time you set goals you can meet you are showing yourself that you can finish things and you can meet your own expectations. It’s a joy double-whammy. 
  • Don’t set yourself up for failure. Be realistic about what you can achieve given your time, energy, and other demands (family, sleep, etc…) Failure has a negative impact on your joy.
  • Sleep. No matter what else you do, prioritize sleep. If you can, take a small dose of melatonin at bedtime. It helps boost serotonin, helps clear excess norepinephrine, and protects your brain from oxidative damage. Also, it improves your sleep
  • Sunlight early in the day. Getting 15 minutes of sun exposure in the morning as early as possible is a great boost to your vitamin D and all of your neurotransmitters. If sunlight isn’t possible, invest in a lightbox or a good full-spectrum bulb.
  • Exercise. Not only is exercise good for literally every health parameter we know about, but it’s also amazing for your neurotransmitters and helps your body to optimize literally every one
  • Balance your methylation. This is all about MTHFR after all…
  • Meditate. If you can meditate regularly, even if it’s just 10 to 15 minutes a day 4-5 days per week, your mental health will change rapidly. This is one of the simplest, quickest ways to hack your headspace. Meditation isn’t just sitting quietly for a few minutes, it’s an active process. There are a ton of great free or low-cost resources out there. When you first start meditating expect to notice your mind getting busier before you notice it getting calmer. That is totally normal.
  • Hold a pencil in your teeth every day for 2 minutes. This forces your body to make a smile, even when you don’t feel like it and smiling boosts your serotonin. Seriously.
  • Trade massages with someone close to you. Or, pay a professional. Human touch and massage are a big deal for neurotransmitter levels, plus it feels awesome. 
  • Listen to beautiful music, appreciate art, appreciate nature, sing, or play. You have so many great options here and each one of them will help to boost your dopamine. Whichever one makes you smile to think about. When you do this activity, do it with your whole attention. Don’t listen to music while you work on the computer – take 10 minutes and really listen.
  • Every time you notice a negative thought, come up with a positive one. Optimism and joyfulness are as much about habit as anything else. We did a whole post on breaking mental bad habits and also what to expect when you’re breaking mental bad habits, and this trick is a simple balancing act. Every time you notice yourself getting down on something, try to find three things you’re happy about or that you appreciate about that thing, person, or situation.
  • Minimize your hassles. A body of interesting research shows that the small things have a much greater impact on happiness than the big things do. That’s small hassles and also small rewards. If you can find ways to minimize your small hassles – like shifting your hours so you don’t drive in rush hour, or taking the extra junk out of your closet so the only clothes that are left are things you truly love, like a capsule wardrobe, it has a significant impact on joy.

These are all small things, and even small things can feel overwhelming when you’re overly anxious, stressed, or depressed. But go through the list and find the one that makes you smile. Maybe you’d like to play and blow bubbles in the park, or maybe the idea of holding a pencil in your teeth for two minutes a day is absurd enough to get a smile out of you. But whatever it is, pick one small thing and do it every day. Every day for at least a month – then let me know how you feel.

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MTHFR and Neurotransmitters – Amy’s Neurotransmitter Theory

These past few weeks we’ve been talking about the link between MTHFR and the production of different neurotransmitters via the BH4 pathway. This includes serotonin and melatonin, dopamine, and norepinephrine and epinephrine.

The research seems to mostly agree that people with mental health issues like depression or anxiety, often have imbalanced neurotransmitters. Somehow, however, that has translated into a locked-in, fixed idea pattern culturally in which depression and anxiety are always neurotransmitter issues and so supplementing or augmenting neurotransmitters is the best path forward medically.

Everyone Agrees Mental Health Is All About Neurotransmitters.

I do want to say that there are people who find a supplement or drug that works for them, stay on the same dose for 15 years, and feel great. There are those cases. These are the shining examples of neurotransmitter-based therapies working and I love seeing them because in the end, it’s a simple solution.

Unfortunately, there are also cases of people chasing down a feeling they had briefly. They get on a drug or supplement, go through the adjustment reactions, it works for six months or a year and then they’re back where they startedmentally, but taking a pill. They increase the dose, increase again, switch to a related drug or supplement and still aren’t where they want to be. They can’t match that time period when the pill was working. They switch to a different class or category of drugs or supplements, and give that a try. Each time with a six to eight-week adjustment window and a host of new or different side effects. I see this all too frequently.

There are several possible problems with the neurotransmitter-only model. We’ll start with the simplest and most obvious problem and work toward more controversial issues.

“Depression” Is a Big Word

And it seems to mean something a little bit different to everyone who says it. Likewise, with anxiety. Over the years I’ve had hundreds of clients tell me they’re depressed. They are always surprised when I ask what that means to them. Not surprisingly, the answer to that question varies greatly.

One man was highly offended at having to educate me about such a basic question. His answer was, “What do you mean what do I mean? I’m depressed! I get up in the morning, the toaster doesn’t work so I slam it on the counter four or five times, and then run out of the door without eating because it’s just too difficult. I’m depressed.” Another client told me she got up in the morning, cried in the shower, cried in the car, smiled all day through her work as a high-level executive, cried the whole way home, then smiled through dinner with her family.

You might notice that the pictures these two people have painted are very different. And these are just two examples out of a seemingly endless variety. The point is, “depression” isn’t something uniform. Sadly, when many people go to their doctor or practitioner and say “I’m depressed” there are only really a handful of standard neurotransmitter-based treatment options for such a myriad of different pictures.

Neurotransmitter Overlap

Another issue I see with the idea of working with mental health from a purely neurotransmitter direction is that the neurotransmitters have significant overlap.

Say you look at something like attention. Serotonin, dopamine, norepinephrine and epinephrine are all heavily involved in attention. Much the same with enjoyment and even alertness. In situations like this engaging in lifestyle changes to actually boost all of these neurotransmitters is a great idea and will help to cover all the bases, but taking a drug or supplement that boosts one pathway leaves plenty of gaps in the system.

It’s obvious, when you look at it this way, that boosting one pathway out of many might lead to imbalances elsewhere that show up as side effects.

It Is Not A Tug Of War

Medicine has become very mechanistic since the advent of penicillin because so many drugs, which do one precise thing in the body, have been lifesaving. I’m all for lifesaving drugs, but this model comes at a cost. We’ve backed ourselves into a corner in which we tend to oversimplify the body into being akin to a constant tug of war between opposing forces or directions of imbalance.

If we suspect serotonin is low – meaning the low side of the tug of war is winning – then we just boost up the other side so it gets higher. Easy. The problem is, neurotransmitters are less like a tug of war and more like a web, with forces pulling at twelve points instead of two. We can, of course, boost up one of those points but it becomes difficult to predict how the other twelve will react and where that will place new stressors on the body.

Your Body Is Smarter Than That

The last issue with boosting a particular neurotransmitter chemically is that for very many people this turns into chasing a dream. Think back to the scenario in the outline where someone started neurotransmitter therapy, had a golden year or nine months, then chased that for the next three years. What happened there?

Well, it is my belief, although this is not a well-researched area, that your body is pretty smart at adapting to the outside world. If your body has set your neurotransmitters at a certain level, and you do something to change that level, I have every faith that your body can reset so that they’re at that same level again, even with the new influence.

The point is, that we’re not getting to the WHY question. WHY did your body set the neurotransmitters at that level to begin with?

Maybe it really is a disfunction or pathology in which your body can’t keep up with production. That is a legitimate possibility (and MTHFR folks – if your methylation isn’t balanced then this is entirely possible because your BH4 pathway is impaired). But what if the problem isn’t production? What if there is a more complex reason for the neurotransmitters being set where they are? What if they are there to compensate for something else that is out of balance?

Your body is the most amazing thing you will ever see, touch, or possess. It is working constantly to return to health, to compensate for damage, to adapt to a dynamic world full of challenges and resources of which you aren’t consciously aware.

So If It Is Not All About Neurotransmitters, Then How Do We Fix It?

The wonderful thing is that working with neurotransmitters is still an option, but this opens up a lot of other options as well. Before you look to neurotransmitters it is important to look to other causes of mental health issues. We did a whole post previously on this topic but some of the more common ones are:

  • Low folate
  • High homocysteine
  • Low thyroid
  • Imbalanced hormones
  • Low testosterone
  • Estrogen dominance
  • Trauma or mental health history

Nobody likes that list because it’s just easier if there’s a pill for it. Sometimes the pills really are the best thing, but it’s a good idea to be open to other types of treatment as well. Be willing to let go of the idea of the magic pill if it just isn’t serving you.

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