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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MTHFR and Norepinephrine

MTHFR can be with mental health issues including depression, anxiety, obsessive-compulsive traits, and global issues like bipolar disorder or schizophrenia.

Culturally, we tend to jump to the idea that all mental health issues are neurotransmitter problems and that the only way to solve them is by boosting your neurochemistry. We’ll explore this idea in a series of posts. You can find the a discussion of serotonin here and information about dopamine here. Today, we’ll discuss MTHFR and norepinephrine, which has the dubious distinction of being both a neurotransmitter, and a hormone.

With mental health issues in a person with MTHFR, it is most important to look first at your methylation because balancing your methylation can produce tremendous changes in your mental health. There are other areas to explore too, like estrogen dominance (this is an issue for us MTHFR folks), low testosterone, or thyroid dysfunction. Still, once you’ve looked at the rest of your health, you may still want to explore neurotransmitters because MTHFR ties directly into neurotransmitter formation via the BH4 pathway. Specifically, the formation of serotonin and melatonin, and the catecholamine neurotransmitters including dopamine, norepinephrine and epinephrine.

MTHFR and Norepinephrine

Norepinephrine and its metabolite, epinephrine, are unique in that although they are primarily neurotransmitters, they also function in the rest of the body as hormones. Neurotransmitters are the method your nerves use to communicate. One neuron sends a chemical signal, the neurotransmitter, across a synapse to another neuron. Hormones are released generally into your bloodstream to affect your tissues.

Norepinephrine and epinephrine are generally associated with the fight or flight response. Although these neurotransmitters do have separate functions, there is significant overlap and so in terms of mental health, it is helpful to think of them in tandem. Generally, more information is available about norepinephrine as a neurotransmitter than about epinephrine so we’ll talk primarily about it. Norepinephrine is also involved in alertness, arousal of interest, pain response, and skeletal muscle function.

Symptoms of Low Norepinephrine

  • Decreased alertness
  • Memory problems
  • Depression
  • Loss of interest
  • Brain fog
  • Fatigue
  • Lack of motivation

Conditions Associated with Low Norepinephrine

  • Fibromyalgia
  • Chronic fatigue
  • Major depressive disorder
  • ADD/ADHD
  • Hypotension, or severe low blood pressure

Boosting your Norepinephrine If You Need To

  • Exercise – as with every other neurotransmitter we’ve talked about, exercise boosts your catecholamines in a healthy way.
  • Meeting Goals – learning to set goals effectively (in a way that allows you to regularly meet them) can provide a huge boost to your norepinephrine.
  • Love – love boosts catecholamines and in a complex way is related to these neurochemicals.
  • Sleep – also as with the other neurotransmitters, sleep is integral in the healthy formation and function of norepinephrine and epinephrine.
  • Cold water plunge – this can double or even triple your norepinephrine levels in just a few minutes.
  • Sauna – if cold isn’t your thing, a sauna can accomplish the same goal, it just takes a bit more time.

Symptoms of High Norepinephrine

Norepinephrine, unlike the other neurotransmitters, is as commonly too high as it is too low.

Like dopamine, can be involved in drug-type “highs” and subsequently this list looks very much like someone who has taken too much cocaine.

  • Tense or spastic muscles.
  • Anxious, fearful, irritable, or racing thoughts.
  • Fear of crowds or small spaces.
  • Insomnia, increased wakefulness, poor sleep.
  • Difficulty concentrating.
  • Changes to blood sugar sensitivity and the way glucose and insulin are produced.
  • Headaches – people with chronic cluster headaches tend to have higher plasma levels of norepinephrine and dopamine, but high norepinephrine may lead to other types of headaches as well.
  • Pounding] heart and increased blood pressure – norepinephrine increases the contractile force of the heart and raises systolic blood pressure.
  • Sweating, generally freaking out.
  • PTSD – recent research has shown that people with PTSD may have an overactive norepinephrine system.

Decreasing High Norepinephrine

Decreasing high norepinephrine is something we all want to happen quickly, but it’s important to give your body time to adjust.

  • Lose weight – a study of obese older men showed that losing about 10 kilos (roughly 24 pounds) resulted in a 31% decrease in plasma norepinephrine levels. Bear in mind this is norepinephrine as a hormone and not as a neurotransmitter, but the levels seem to rise and fall at the same time.
  • Cognitive Behavioral Therapy – Cognitive behavioral therapy operates on the idea that people who have had long-term stress have developed ways to cope with that stress, and helping them to learn healthier ways, will have a positive impact on their levels of anxiety, perceived stress, and also their neurochemistry.
  • Melatonin + Lying down – Melatonin, mostly known as the sleep hormone, also helps to balance norepinephrine levels, but only if you take it and then lie down. Since it’s the sleep hormone, it’s probably best to do this at bedtime.
  • Meditate – Meditation packs a punch in terms of reducing stress and balancing neurochemistry.

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Dopamine and MTHFR

MTHFR can come with a whole host of mental health issues including depression, anxiety, obsessive-compulsive traits, and broader issues like bipolar disorder or schizophrenia.

Culturally, we tend to jump to the idea that all mental health issues are neurotransmitter problems and that the only way to solve them is by boosting your neurochemistry. We’ll explore this in a series of posts. You can find the first one, on serotonin, here. Today, we’ll discuss dopamine and MTHFR.

With MTHFR especially, it is most important to look first to your methylation and work on balancing that because balancing your methylation will produce tremendous changes in your mental health. There are other areas to explore too, like estrogen dominance (this is an issue for us MTHFR folks), low testosterone, or thyroid dysfunction. Still, once you’ve looked at the rest of your health, you may still want to explore neurotransmitters because MTHFR ties directly into neurotransmitter formation via the BH4 pathway.

Dopamine and MTHFR

Dopamine release is pleasurable and is associated with feelings of reward, so dopamine is tied into learning and motivation. The more dopamine a particular activity causes to be released, the more motivated we are to engage in that activity. Likewise, if only low levels of dopamine are released then we lack the happy reward feelings and are not very motivated to try that activity again. Dopamine is also involved in the regulation of body movements, and very low dopamine is linked to both Parkinson’s disease and schizophrenia.

Symptoms of Low Dopamine and MTHFR

While low dopamine can express as a mental health issue, the first signs might not actually be related to mental health. Also, symptoms of low dopamine can be an issue with the actual level of dopamine, but more commonly it is an issue with the levels of dopamine receptors, which are also susceptible to fluctuation.

  • Persistent constipation – Dopamine in the spinal nerves may be linked to the healthy movement of the GI tract.
  • Low enjoyment – Because dopamine produces feelings of reward, low dopamine can make you stop enjoying the things that used to make you happy.
  • Tremors, shaking hands, restless legs, or muscle twitches – Dopamine’s involvement in regulating muscle function means that low dopamine can affect these systems first.
  • Difficulty swallowing or aspiration of food – The muscles that control swallowing are also regulated by dopamine and are very small muscles with major functions. Decreasing dopamine levels can make it more challenging for this system to function the way it should.
  • Decreased sex drive – Just like dopamine is involved in reward with other activities, it’s involved with the feelings of reward that we get from sex as well.
  • Addictions – For some people, a low sense of reward can lead to addictive tendencies. Especially with drugs powerful enough to trigger that sensation.
  • Fatigue and lack of wakefulness – Dopamine is one of the reasons you feel refreshed and alert most mornings. Low dopamine or low dopamine receptors leaves you feeling groggy, fuzzy, or sleepy.
  • Weight gain – especially after periods of high dopamine stimulation, like the weight gain that follows smoking cessation. Essentially, chasing the same dopamine levels leads to overeating.
  • ADHD – research is beginning to show a link between low dopamine states, genetic polymorphisms relating to dopamine receptors, and ADHD.
  • Major depressive disorder
  • Schizophrenia
  • Parkinson’s disease

Obviously, dopamine is vital to health and wellbeing.. The biggest and most important step for MTHFR folks is going to be balancing your methylation. That means following the To Health WIth That Plan – eliminating folic acid, getting a background of good B vitamins without any folate or B12, then slowly adding in methyl folate and a good form of B12 one at a time. All of this while using your symptom tracker. If the plan is new to you, we’ve got a great “Start Here” resource for you.

Once you’ve got your methylation levels where you want them with methyl folate or folate alternatives, it’s time to address dopamine specifically. Here are some things you can try.

  • Exercise – running, dancing, or otherwise working up a sweat can push dopamine levels in certain parts of the brain, leading to the characteristic “runner’s high.”
  • Sleep sleep deprivation has been shown to reduce the number of dopamine D2 receptors in the brain, and restoring healthy sleep can replenish those numbers.
  • Losing weight – Research has shown that obesity also reduces the number of D2 receptors relative to normal. Losing weight could help to boost those receptors again.
  • Listening to music, seeing beautiful art, singing, or playing – while the survival benefit to feelings of reward from food or sex is pretty clear, this is a bit more mysterious. Uplifting or beautiful music, enjoyment of art, singing, or engaging in play stimulate the same feelings of reward via dopamine and can be used to bolster flagging levels.
  • Eat your dopamine – bananas, avocados, and plantains are good dietary sources of dopamine, and banana peel is almost 100 times richer a source than banana pulp, so maybe it’s time to make some organic whole banana smoothies. Also, eating good food sources of tyrosine, which is the precursor to dopamine, can be very helpful. These include chicken, almonds, peanuts, soy, and dairy products.
  • Reduce your stress levels – chronic exposure to stressors lowers neurotransmitters globally, including dopamine. Learning how to reduce or manage your stressors can change those levels for the better.
  • Eat less saturated fat – saturated fats like those in butter, animal fat, coconut oil, and palm oil can disrupt dopamine levels when eaten at high levels. Research shows that the changes in dopamine levels happen even without changes to weight, hormones, blood sugars, or body fat.
  • Meditate – One study showed a 64% increase in dopamine response after an hour of meditating vs an hour of sitting quietly. 64% is a whopping increase, and although an hour of meditation might not fit into everyone’s daily routine, I’m guessing you could find 15 minutes.
  • Sunlight or a light therapy box – Dopamine D2 and D3 receptor levels are much higher in people with higher sunlight exposure than they are in people with low sunlight exposure. Getting more light can boost your receptor profile.
  • Mucuna pruriens – Mucuna pruriens, otherwise known as velvet beans have a high level of L-dopa, the direct precursor to dopamine. Studies on Mucuna for Parkinson’s disease show that the benefits of Mucuna might be both stronger and longer lasting than those of traditional medications for Parkinson’s disease. Velvet beans are toxic in high amounts so always work with a practitioner to find a good dose for you.
  • Tyrosine supplements – Tyrosine, taken away from food can give your body a good supply of precursors to feed your dopamine pathway.

Neurotransmitter balance, including dopamine levels, depends strongly on your methylation, and balancing methylation is your foundational step. Once you’ve laid the foundation, addressing receptor function should be your next priority. Lifestyle changes that boost your receptors like getting good sunlight exposure, meditating, and making dietary changes, will be far better in the long run than taking supplements unless you’re in an extremely low dopamine situation like Parkinson’s or schizophrenia.

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Serotonin and MTHFR

MTHFR can come with a whole host of mental health issues including depression, anxiety, obsessive-compulsive traits, and more major states like bipolar disorder or schizophrenia.

Culturally, we tend to jump to the idea that all mental health issues are neurotransmitter problems and that the only way to solve them is by boosting your neurochemistry. We’ll explore this in a series of posts.

That idea, however neat and tidy, is just not true. With MTHFR especially, it is most important to look first to your methylation and work on balancing that because balancing your methylation will produce tremendous changes in your mental health state. There are other areas to explore too, like estrogen dominance (this is an issue for us MTHFR folks), low testosterone, or thyroid dysfunction. Still, once you’ve looked at the rest of your health, you may still want to examine those neurotransmitters. So let’s dive in and learn what we can about the highs and lows of particular neurotransmitter states. Especially since MTHFR ties directly into neurotransmitter formation via the BH4 pathway.

Serotonin

Serotonin helps to stabilize and modulate your mood, gives you feelings of well-being, and boosts joyfulness. It’s also involved in processes such as memory, feeling of reward, learning, and cognition. Interestingly, serotonin also has a heavy impact on digestion, with 80 – 90% found in the gut helping to regulate intestinal motility. Serotonin is also involved in such diverse processes as vasoconstriction and clotting. Given that it has so many functions, it is easy to see why problems show up vividly.

Symptoms of Low Serotonin and MTHFR

  • Depression – Although people think of this as an obvious statement, the research on serotonin and depression is actually quite mixed. Also, life events that typically cause depression, like chronic stress and trauma, have been shown to deplete serotonin levels. So while low serotonin might be a causative factor in depression, it might also be a consequence of difficult life events that cause depression.
  • Chronic Pain – Low serotonin is highly correlated with chronic pain states like fibromyalgia and many people with fibromyalgia report benefits from serotonin-boosting supplements or drugs. This could be because serotonin has the ability to strengthen the brain’s signals to the muscles. Also, conversely, if it’s in too large amounts it can make muscles like the muscles in your legs feel heavy.
  • Memory or Learning Issues – Sudden issues with memory or learning could signal a drop in serotonin.
  • Anxiety – Anxiety that appears without an obvious trauma or stressor, or anxiety that includes an obsessive-compulsive component, could well be a serotonin issue.
  • Internal Clock Problems – Serotonin along with its metabolite melatonin help to regulate your circadian rhythm. Not sleeping according to a regular schedule, having difficulty keeping a regular schedule of hunger and eating, or feeling chronically tired or constantly hyper might indicate a serotonin deficiency.
  • Sleep Trouble – Because of its relationship with your internal clock and your sleep hormone melatonin, serotonin is all tied up with your sleep. Serotonin deficiency may show up as chronic insomnia, unusual sleep patterns, chronic fatigue, or consistently vivid dreams might have low serotonin.
  • Appetite Irregularity including Eating Disorders – Low serotonin symptoms may include overeating, not eating enough, or alternating between those two states.
  • Dementia – Because of its link with memory and cognition, serotonin may play a role in dementia as well. Studies certainly show a link with early dementia but it is unclear whether low serotonin is a cause or a symptom.
  • Hyperactivity – A link exists between serotonin and ADD or ADHD People with low serotonin might fidget constantly, feel restless or agitated, or be chronically bored.

Obviously, serotonin is a big deal for your body and certainly something that you want to have enough of. In good news, working with serotonin and MTHFR gives you some really direct routes to addressing issues. The biggest and most important step for MTHFR folks is going to be balancing your methylation. That means following the To Health WIth That Plan – eliminating folic acid, getting a background of good B vitamins without any folate or B12, then slowly adding in methyl folate and a good form of B12 one at a time. All of this while using your symptom tracker. If the plan is new to you, we’ve got a great “Start Here” resource for you.

Once you’ve got your methylation levels where you want them with methyl folate or folate alternatives if you don’t tolerate folate, it’s time to address serotonin specifically. Here are some things you can try.

  • Melatonin at bedtime – Melatonin is made from serotonin, so if you’re supplementing at bedtime, it can leave you with more serotonin left over. Plus, it helps to improve sleep quality and makes falling asleep easier. It’s also a great antioxidant that crosses the blood-brain barrier, which is a total bonus.
  • SAMe – If you’re already working on methylation, SAMe might already be something you’re familiar with. If it isn’t, it can be a good boost to the BH4 pathway that helps your body to crank out the neurotransmitters. Just be careful and raise your dosage slowly because, just like methylated B vitamins, SAMe can cause reactions for MTHFR folks if we take too much, too quickly.
  • St John’s Wort – This potent herb has been incredibly well documented as an aid in depression, and it is documented to raise serotonin. In fact, research shows that when you compare St. John’s Wort to conventional SSRI medications, which are the most frequently prescribed medications for depression in North America, the results are very similar.
  • Aerobic exercise – Serotonin is made from an amino acid called tryptophan, and doing light cardio that you enjoy triggers the release of tryptophan into your blood and decreases the levels of other amino acids, hence getting more tryptophan to your brain. For an added boost, do something that makes you happy.
  • Sunshine or a light therapy box – Bright light boosts serotonin, and research has been suggesting that some might be made in our skin in response to light. If you combine your exercise with sunshine it could give you a double whammy, but if that isn’t possible, there are also light therapy boxes that can help if you have a hard time getting into the sun.
  • Massage – This doesn’t have to be anything fancy. A study of depressed pregnant women showed that 20 minutes of massage from a partner twice a week boosted their serotonin and dopamine levels and decreased the stress hormone, cortisol (along with back and leg pain).

All of this boosting is great, but I do want to give you a quick warning about serotonin syndrome, which can happen if you take serotonin-boosting supplements on top of some antidepressants, or even too many supplements. Serotonin syndrome is serious and can be life-threatening if untreated. If you’re already taking an antidepressant, or if you wish to swap out your current medication for natural methods, please talk with your doctor to develop a safe plan to do so.

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MTHFR and Decision Fatigue

We’ve had a number of heavy topics lately and I wanted to lighten it all up a bit this week by talking about something that is sorely needed for many MTHFR folks. That is ease. Ease, ironically, is something we don’t tend to do easily, especially when it comes to self-care.

The joy and devastation of the internet is that it offers every human looking around an infinite variety of opinions, an infinite number of ways to take care of themselves, and every conflicting idea in its full glory. This leaves us with an unmanageable amount of information to sift through and the burden of a ridiculous number of decisions about the best way to care for ourselves. In short, self-care requires not only the time and energy that is needed to actually exercise, eat good food and do your things, but also the mountain of time and energy needed to figure out what those things should be.

Unfortunately, “because your mother told you to” is not the rationale most people use in their decision tree on this topic unless their mother happens to be a brain surgeon, PhD, actor, or social influencer. Those are the voices we listen to these days and in some ways that is beneficial, but it becomes a clamor of 1000 voices rather than one.

Decision Fatigue

Decision fatigue is the mental and emotional strain resulting from the burden of choices. It often feels like a deep sense of weariness and can be a red flag that you’re headed for burnout. Burnout happens in self-care as easily as it happens at the office and it shows up in some potentially familiar ways.

  • Procrastination – “Nevermind, it isn’t due until Friday…”
  • Avoidance – “I just can’t deal with this today.”
  • Impulsivity – “Cooking is hard, but chips are easy.”
  • Indecision – “Oh, I don’t know. You choose.”

It’s not just the giant life-choice decisions that weigh heavily. It turns out the little ones do too. Are you wearing brown or red shoes? Will it be oatmeal, eggs, or cereal? Will you start the laundry or leave it? None of these decisions have any consequence at all, but all of them produce anxiety and require resources. The same resources have to be used for the big stuff like Should I have that procedure? Do I need to call a specialist? Or can I fit physiotherapy into my budget? Actually, just reading the list of questions is exhausting, let alone making the decisions.

In a situation like MTHFR, there isn’t truly a one-size-fits-all path forward. It’s a very individual journey and that can increase the likelihood of decision fatigue.

In good news, there are some things you can do to minimize the decision fatigue around MTHFR, make it all a little easier and free up some resources to use in other areas of your life.

Tips To Avoid the MTHFR and Decision Fatigue Problem

  1. Find your trusted source – the internet is awash with opinions, right ways forward, testimonials, and products that are miracle cures. Find one voice you trust and actually try their program, protocol or suggestions. Mixing and matching is a great idea in your wardrobe but doesn’t work so well with health management strategies. Also, this cuts down on the random “Dr. Google” ideas.
  2. Stop talking to “Dr. Google” – once you find the voice you trust, stop searching for more unless you decide to choose a different voice and follow a different path. Let one system be enough and don’t continue to search and search. Too often people don’t get the benefits of one plan because they are constantly adding in other things. It’s like mixing diets in the style of Bridget Jones.
  3. Change one thing at a time – with MTHFR, there is a tendency to have challenging or unexpected reactions to supplements or diet changes. By only changing one thing at a time and giving your body at least a week to two weeks between each change to your self-care routine, you can actually sort out which changes are useful and helpful and which ones aren’t.
  4. Streamline what you’re currently doing – this is a step that is so often overlooked and it really matters for everyone, not just for people with MTHFR issues. At least quarterly, sit down and take stock of your health habits. This includes prescriptions and supplements that you are taking, exercise, diet strategies, self-care, and practitioners. Do this on a day when you have some time and energy to spare. Be willing to let go of things that aren’t working so that you aren’t just adding more ineffective strategies to a heap of ineffective strategies you already have. Make the things you do for your health, count because they all take time, energy, and money. Talk with your doctor if there are prescriptions that might no longer be needed or that aren’t actually solving the problem they were intended to solve.
  5. Use the 80-20 rule – this aphorism tells us that 80% of your results come from 20% of your actions. I believe this applies to your health as well. Can you find the few health actions you’ve taken that are giving you your 80% and double down on those? Even better, can you let go of some or even all of the rest? I can easily tell you my 20%:
    1. Eating wheat and folic acid-enriched product-free.
    2. Prioritizing sleep and sleep hygiene.
    3. Magnesium every night
  1. Do fewer things better – doing fewer things for your health but doing them really well is far better than doing more poorly. Sticking to a diet, prioritizing sleep, and taking a multivitamin is going to be far more effective than doing a diet, detox, new exercise program, mindfulness routine, and 18- pill per day supplement program that you get right one day out of five. Pick your battles.
  2. Focus on one problem – every little symptom probably doesn’t need its own plan. Focus on one big problem like energy or sleep and let smaller stuff go.

Not only will this make each day a little bit easier, but it will also add up to better results with your health. Never underestimate a clear path forward and the power of doing only a few things, well.

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Fish Oil and MTHFR, What Is The Link?

We’ve all heard about fish oils and omega3 fatty acids for so many incredible reasons. They are strongly anti-inflammatory and perform almost as well as non-steroidal anti-inflammatory tests for pain relief, without side effects. 

They have been most strongly studied for heart disease and show an almost unbelievable array of benefits. Fish oils reduce the risk of sudden death from cardiac arrhythmias, reduce all-cause mortality in patients with known cardiac disease, and help to treat high cholesterol (hyperlipidemia) and high blood pressure (hypertension.) All of this, without significant side effects or drug interactions

Studies have also shown that countries with higher intake of omega-3 fatty acids have lower rates of depression. Fish oils have also shown beneficial effects in both research and clinical practice for diabetes, Alzheimer’s disease, stroke, and autoimmune disease. 

What about Fish Oil and MTHFR?

Most studies aren’t MTHFR-specific.  But, fish oil has benefits for so many of the long-term consequences of unbalanced methylation in MTHFR, that it makes sense that there would be some link.  What reserach has found is some kind of synnergy between fish oil and B vitamins, in which the combination works better than either therapy alone.

Omega-three fatty acids and B vitamins for cognitive decline

A randomized placebo-controlled  trial of people with mild cognitive impairment found that treatment with B vitamins lowered homocysteine and slowed the rate of cognitive decline. Researchers went back and re-analyzed the data from this study to see if baseline levels of omega-three fatty acids interacted wtih the results in any way. The study involved mental testing over the course of two years.They found that for all outcome measures, higher concentrations of DHA significantly enhanced the effects of B vitamins, while the levels of EPA had less of an impact.

Not only that, when omega-3 fatty acid levels are low, B vitamin treatment has no effect on cognitive decline, but when omega threes are in the high-normal range, B vitamin treatment becomes effective. There is some synnergy happening here that needs further investigation to fully understand, but since omega-three fatty acids are good for so many things and truly haven’t shown negative consequences it makes sense to add them in as a no-risk measure for seniors with cognitive decline.

Omega-three fatty acids and homocysteine

The methylation process itself seems to be involved in the metabolism and distribution of these polyunsaturated fats through your body, which means that MTHFR and omega-3s are intimately linked. Also, it has been theorized that omega-three fatty acids actually have expression control on enzymes within the methylation cycle, so effectively MTHFR controls omega-threes, which control MTHFR. There is not a big enough body of research yet to draw firm conclutions, but the evidence is pointing in this direction.  For MTHFR folks, the most important thing to understand is that using fish oils and B vitamins together produces a great reduction in homocysteine levels than using either one alone. 


This research suggests that omega-3 fatty acids (referred to here as PUFA or polyunsaturated fatty acids) actually stimulates the action of the MTHFR enzyme, which activates folate to generate SAMe, the methyl donor. PUFA also stimulates the MAT enzyme which converts methionine to SAM, the CCT enzyme which is involved in the conversion of choline to phosphatidylcholine, and the CGL enzyme which is involved in the conversion of Homocysteine to Glutathione. 

Inflammation, heart disease, cognitive decline, and high homocysteine are all problems that happen more frequently in folks who have MTHFR with unbalanced methylation, and since fish oils effectively address these problems, it almost seems like a gimme.

Next week, we’ll talk about a few bits of research being done regarding fish oil and gene expression for MTHFR folks. The research is new, but it’s starting to get good.

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What To Expect When You’re Breaking A Mental Bad Habit

Last week we started our conversation about the “bad habit” component, called neuroplasticity, of depression, anxiety, intrusive thoughts, and obsessive or compulsive thoughts. This is, of course, only part of the picture. Neurotransmitter balance is a factor along with the often overlooked physical contributors to depression and other states.


We discussed three main methods for breaking mental bad habits. Those are:

  1. The Fantasy
  2. The Stop and Drop
  3. The Distraction

When you’re first trying this, it can be really helpful to try all three strategies at different times to see what works the best for you. You’ll know it works when you are able to pop yourself out of your mental bad habit – to feel different in your body and to let go of whatever thought pattern it is that you’re working on.

Stages of Resolution With Mental Bad Habits

  1. Learning. In this phase, you’re actually learning to pay attention to your thoughts and that takes more time than you would think. You may find a particular “warning” signal for you – it could be a behavior (like when I’m starting to feel this way I always log on to Facebook and click links that make me angry or I start craving XYZ food. It could also be a physical feeling – a headache in a particular place, a clenching in your belly, pain in your neck or shoulders. It could also be something more subtle like tuning into your mood more frequently.
  2. Out of Control. This phase feels like you’re moving backward. You’ve started tuning in and now you’re actually noticing how much your brain does this thing and it’s a ton! It will seem like your brain is a wild horse racing ahead of you, and it feels like the bad habit is happening more, not less.  That is a GREAT sign because the reality is that you aren’t doing the bad thing more, you’re just noticing more and that is the first step to actually changing it. This can take a few months of diligent attention, but don’t get discouraged – you’re doing it and you’re making progress.
  3. Quietening. In this phase, you start to make tangible progress and you’ll notice that the mental bad habit becomes softer somehow. Quieter.  The thoughts/feelings are still there and they still affect you, but you’re learning to let them go more quickly and it’s easier not to get pulled in by them. 
  4. Maintenance. This phase is amazing.  One day you’ll notice your mental bad habit pop up and the first thought you’ll have is “Oh! I haven’t seen that for a while.” and you’ll dismiss it and move on. This is the phase where you have the freedom to move on to something else because that bad habit is mostly gone.  It’s a good idea to still take proactive action when it pops up, but it is popping up so much less frequently that it becomes almost a curiosity when it’s there.

Great! So I’ll be mentally healthy by next week, right?

Absolutely not. I would love to say it was easy and took no time or effort, but that would be a bald-faced lie. It’s a challenge and it takes time. You’ve probably had this mental bad habit for years if not for your entire adult life, so it will take some time to break it too. And some time doesn’t mean a couple of weeks, it means months and maybe even a year. This isn’t quick, but it is SO. WORTH. IT.

Does This Work Every Time?

This works every time if you stick with it, and when there isn’t some other major imbalance. If your serotonin is actually so low it’s living in the sub basement, then this will still help fix the habit part of it, but it won’t completely normalize the serotonin (but it will bring it up – research shows these techniques are associated with higher levels of both serotonin and melatonin). Although, every day we’re learning more about what this can actually accomplish.

What IS This Witchcraft? It’s Mindfulness.

Yup. That thing that hippies and new-agey types do. Also, everybody who studies neurology and neuroscience of any sort, because as it turns out the effects are so powerful as to be almost unbelievable.

Among the many documented effects of any form of mindfulness are:

  • Increased wellbeing
  • Reduced cognitive reactivity (so external things don’t affect you so much)
  • Reduced inflammation
  • Reduced reactivity of the autonomic nervous system (you don’t get an adrenaline spike every time something bad happens)
  • Higher serotonin
  • Higher melatonin
  • increased telomerase activity (anti-aging)
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