Recent Episodes

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.

Share with friends:

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.

Share with friends:

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.

Share with friends:

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.

Share with friends:

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.

Share with friends:

The Best B12 For MTHFR

This question seems to come up frequently in the MTHFR community, Genetic Rockstars.  And of course, B12 levels have a lot to do with how you feel and how well you’re methylating on a daily basis, so it’s a really relevant conversation. Vitamin B12 is a cofactor in the recycling of homocysteine to methionine and in the generation of SAMe, which is the primary methyl donor, so it is something that every MTHFR mutant out there should be thinking about.

There are four commonly available forms of vitamin B12. The easiest to find and cheapest is cyanocobalamin, which is cobalamin, or B12, bonded to a cyanide carrier.  Methyl B12 is the active form and needs no interconverting to be useful by the body. It is already bioavailable and active.  HydroxoB12 is cobalamin bonded to a hydroxyl group, which is just oxygen and hydrogen and doesn’t require a lot of resources to detox.  Adenosyl B12 is cobalamin carried by an adenosine, which is also useful in the body. 

It seems really simple to say “of course, methyl B12 is the best for MTHFR folks – we have trouble methylating things and it’s already methylated, so this seems done and dusted.” And it is, for the most part. The issue is that in some cases, methyl B12 is too stimulating in the way that taking 5-LMTHF or methyl donors like TMG can be too stimulating. It’s just too quick a rush of too many good things at once and your body kind of freaks out. It’s technically “the best” but also can feel not so good. Let’s break down the forms one by one.

Cyanocobalamin

Cyanocobalamin is the cheapest to produce, cheapest to buy, most readily available, and easiest to store – it’s heat stable and resilient. It doesn’t absorb particularly well when taken orally and it does require a methyl group to convert into an active form. Also, your body has to actively detoxify the cyanide molecule. Cyanide has a big reputation as a toxin, but this is a very tiny dose. Also, absorption decreases if there are any compromises to stomach acid levels, which is a common problem in the Western world, as evidenced by the number of people taking medicines for reflux, heartburn, and the like.

For people with severely compromised methylation – like kids on the autism spectrum, symptoms can actually get worse, instead of better, with this form of B12 because it does require methylation and methyl groups are in such short supply.

Also, a small study that used radioactive markers on cyanocobalamin, showed that it takes more than 48 hours for cyanocobalamin to convert to methylcobalamin, which in terms of typical vitamin use, is extremely slow.

Overall, if there is no other source of B12 available then cyano is better than nothing, but if you have another choice, a different form is better.

Methylcobalamin

Methylcobalamin is the active form of B12 and requires no interconversion to be used by your body. This is by far the best form for any issues involving degenerative neurological processes and can help relieve or reverse symptoms. It is a widely accepted adjunct therapy for peripheral neuropathy, Alzheimer’s dementia, Bell’s palsy, and other neurological disorders. It promotes growth, regeneration, and myelination of the nerves.  


Methylcobalamin has also been studied along with adenosylcobalamin for anti-tumor effects and to inhibit the proliferation of various cancerous cell types. Methylcobalamin helps to lower homocysteine levels and has even been used experimentally to inhibit the HIV-1 virus in human white blood cells. Additionally, methyl B12 may help with the methylation of serotonin to melatonin, your body’s sleep hormone and for some people, it improves sleep tremendously. Obviously, this form is a bit of a rock star.


For MTHFR folks, if you tolerate methylcobalamin, it’s a great choice, but some of us don’t tolerate the rapid absorption and rapid utilization. For people who have trouble, it can lead to feelings of anxiety, agitation, excitability, or insomnia.  

Hydroxocobalamin

This is another inactive form of B12, and it is the form found most commonly in food sources. It is not bonded to anything toxic, the hydroxo group converts harmlessly to water.  Compared to cyanocobalamin it bonds more easily to plasma protein and has a longer half-life in the blood.

When you take methylcobalamin and it uses its methyl group for something, it actually converts in the body to the hydroxocobalamin form, so these two interconvert easily, depending on whether or not they’re methylated. Taking the hydroxo form just means you need to use methyl donors to activate the B12, while taking the methyl form means it’s bringing its own methyl groups with it.  Interestingly, hydroxocobalamin can scavenge nitric oxide, which is one of your body’s main vasodilators, and so it isn’t the best form for people with hypertension.

Adenosylcobalamin

Adenosylcobalamin is the other active form of B12, which is the predominant form that your body stores as B12 reserves in the liver. This is also the form that is used primarily in the mitochondria, which generate your cellular energy. Adenosyl is a great form especially in cases of people with liver issues.

There are some cases of chronic fatigue in which people only really feel better with adenosylcobalamin. They notice an increase in energy with this form but no other. This is thought to be due to a problem interconverting between the forms. If you notice a big difference with the adenosyl form it can be beneficial to look for a mixture of both adenosyl and methylcobalamin.

Share with friends:

Gene Expression, Fish Oil, and MTHFR.

Fish oil, which we talked about last week as well, continues to be a big deal for people with the MTHFR mutation. Today, I want to discuss a couple of studies about gene expression, fish oil, and MTHFR, but first I want to make sure everybody understands the basics of gene expression.

When your body makes something out of your genes, it doesn’t just read the DNA and make a protein. There is more to it than that. The process, however, can be broken down into two big chunks – bear in mind that there is far more to it than this as well, but this will help you to understand the research we’re going to talk about..

  1. Transcription -Transcription is the process in which the DNA is opened like a zipper and mRNA is made from one side of the zip, and the resulting mRNA molecule is processed by the body.
  2. Translation – Translation occurs when the mRNA molecule we made above, is used to direct protein synthesis. This is how the MTHFR gene makes the MTHFR enzyme, which is the protein this gene codes for.

mRNA is genetic material just like DNA, but the difference is that while DNA might be the ultimate blueprint, it is also giant, double-stranded, and not easy to work with. RNA of all types, including messenger RNA, is single-stranded and generally transcribed from the master DNA. It is created in small segments and is the signal needed for your body to actually build proteins.

What this means is that mRNA is a good marker, in research, specifically this research about fish oil and MTHFR, for the action of the MTHFR gene and one of the only ways we can measure when the gene is acting.

Gene expression in the homocysteine cycle with Fish Oil and MTHFR

Last week we mentioned that levels of fish oil and homocysteine were linked – the higher the fish oil intake for the person studied, the lower homocysteine levels became. Let’s expand on that.

This study, published in Nutrition Journal, looks at the gene expression, meaning the mRNA levels for different enzymes along the homocysteine pathway. This includes MTHFR, but also other enzymes including MAT, CSE, SAHH, CBS, and MTR. See the diagram to place each enzyme within the pathways for recycling and converting homocysteine.

Human liver cells were treated with either decosahexaenoic acid, DHA, eicosapentaenoic acid, EPA, or alpha-linolenic acid, ALA for 48 hours. A control group with no treatment was also kept for 48 hours and then studied. After that time, mRNA levels were measured from each enzyme in question. It was found that:

  • MTHFR was upregulated by both DHA and ALA.
  • MAT was down regulated by all three treatment groups, but most in the DHA group.
  • CSE expression was increased in the DHA and EPA groups.
  • No significant changes were shown in SAHH, CBS, or MTR.
Omega-3 fatty acids like EPA, DHA, and ALA have an effect on the action of certain gene SNPS and the enzymes they code for.

This study is remarkable because it shows that the action of MTHFR can be influenced with something as simple as fish oil. The next study is even more remarkable.

Pregnancy, Fish Oil, and MTHFR

Methylation is one of the primary drivers of a person’s epigenetic state, and some of the most important methylation happens during gestation, so research involving this period is especially important. This particular study, published in Biomedical Research International, was conducted on rats.

Because previous research has shown that nutritional changes in the mother affect both poly-unsaturated fatty acid metabolism and global methylation in the placenta. This study theorized that the changes are due to some regulation of the maternal enzymes in the methylation cycle by dietary nutrients.

This study divided pregnant rats into six groups.

  • Normal folic acid and B12 (this is the control group)
  • Normal folic acid, B12 deficient
  • Normal folic acid, B12 deficient with omega-3 fatty acids
  • High folic acid, normal B12
  • High folic acid, B12 deficient
  • High folic acid, B12 deficient with omega-3 fatty acids

Placental mRNA levels were tested for MTHFR, MTR, MAT2a, CBS, PEMT, and GAPDH. Placental glutathione and phospholipid analysis were also performed.

In an effort to not bore your pants off, I’ll get to the relevant details about MTHFR.

As expected the mRNA expression of MTHFR was decreased in both B12 deficient groups relative to the normal B12 groups. Interestingly, omega-3 fatty acids were able to return the mRNA to a normal level in the normal folic acid, B12 deficient group but not the high folic acid, B12 deficient group.

This tracks with what we know about folic acid’s double-edged effect on the MTHFR enzyme. A small to normal amount is good (and far better than no folate intake) but too much inhibits the MTHFR enzyme

Placental glutathione levels followed much the same pattern. In the normal folic acid, B12 deficient group the glutathione levels were lower than normal (although not statistically significant). With excess folic acid however, glutathione levels with higher in those rats with normal B12 and significantly lower in the rats with B12 deficiency. Omega-3 fatty acids were able to correct the glutathione level in the normal folic acid, B12 deficient group but not in the excess folic acid group.

My theory about this is that glutathione manufacture is more difficult in the presence of imbalanced folate or B12, but that it increases in the most imbalanced group, which is excess folic acid and deficient B12, in an effort by the body to protect itself with glutathione buffers against increased oxidative stress.

Phospholipid levels tested higher in both B12 deficient groups compared to the control group. In both of those groups omega-3 supplementation reduced them.

This study is so remarkable because we’re looking at the time period when epigenetic is at it’s most potent and when the protective effects of omega-3 fatty acids could potentially alter the course of these pregnancies. While placental levels are being measured, these changes may have an impact for the developing fetus as well. This means that even in the presence of a somewhat unbalanced diet leading to unbalanced methylation, omega-3 fatty acids offer a regulating effect and may mitigate some of the worst of the consequences of the unbalanced diet.

Thus, the metabolisms of folic acid, vitamin B12, and DHA are interdependent on each other possibly through the one-carbon methyl cycle.

Khot V, Kale A, Joshi A, Chavan-Gautam P, Joshi S. Expression of genes encoding enzymes involved in the one carbon cycle in rat placenta is determined by maternal micronutrients (folic acid, vitamin B12) and omega-3 fatty acids. Biomed Res Int. 2014;2014:613078. doi:10.1155/2014/613078

Share with friends:

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.

Share with friends:

Lowering Homocysteine with MTHFR

As with everything to do with MTHFR, balancing your methylation and boosting your B vitamins, especially B2, folate or 5-LMTHF, and B12, is the first step. Balance your methylation! There are some other things you can look into as well.

MTHFR Isn’t The Only Cause of High Homocysteine

Of course, our focus is MTHFR, but high homocysteine has other causes as well and the sad truth is, you can have fleas and ticks on the same dog. That is one of my favorite Texas expressions. What I mean by that is that just because you have MTHFR, doesn’t mean you don’t have to also watch out for other causes of high homocysteine. It’s important to manage those too. Other Causes of high homocystein (or hyperhomocysteinemia) include:

  • Poor diet
  • Poor lifestyle
  • Smoking
  • Diabetes
  • Rheumatoid Arthritis
  • Thyroid imbalance
  • Chronic inflammatory diseases
  • Celiac disease
  • Crohn’s disease
  • Long-term use of corticosteroids
  • Prescription medications
    • methotrexate (because it lowers folate)
    • metformin (long term use because it interferes with B12 absorption)
    • hydrochlorothyazide
    • Fibrate type cholesterol-lowering medications
    • Levodopa
    • Anti-epileptic drugs (long-term use)
    • Possibly nicotinic acid or niacin, but research is very conflicted.

If you have one of these underlying conditions or are taking a medication known to elevate homocysteine, then working on that condition or talking with your physician about the medication can be a great place to start. Outside of that, let’s talk about useful steps.

The MTHFR Plan to Lower Homocysteine To Optimal

  1. Balance your methylation – I’ve said it already, but the first step is always boosting your methylation cycle because this is where we tend to stall out with MTHFR. This means following the To Health With That! Plan. Eliminate folic acid, add a methylation-friendly B complex, then add 5-LMTHF, or folinic acid, or whatever workaround you are using if you don’t tolerate folate. If you aren’t familiar with the plan you can start to walk through it here.
  2. Limit your protein intake – The more protein (and consequently methionine) you take in, the more homocysteine your body makes. There’s a full article about the methionine and homocysteine link here.
  3. Quit smoking – As though you needed one more reason why smoking is bad for your health. But yes, smoking raises your homocysteine levels.
  4. Take a look at your alcohol intake – alcohol blocks folate absorption, and so increased drinking can raise your homocysteine levels. This is probably mitigated by extra folate intake, but possibly not.
  5. Balance your coffee intake – As much as it pains me, too much coffee has consequences and high homocysteine is one of them.
  6. Zinc – zinc is a cofactor in some of the enzymes involved in the recycling of homocysteine to methionine, and so zinc deficiency can increase homocysteine levels while zinc supplementation can help to improve beneficial conversion.
  7. NAC – NAC, or N-acetyl cysteine, has been shown to lower homocysteine levels as well as folate supplementation in studies.
  8. Fish oils – in a magical synergy, fish oils + B vitamins work better together than they do apart.
  9. Make sure there aren’t other underlying causes – If you’re doing everything right and your homocysteine still isn’t where you want it to be, it matters to talk to your doctor about other underlying causes. If you’re living the perfect lifestyle, but you still have a low thyroid, then fixing your thyroid is probably the only thing to bring your levels back to balance.

Don’t forget that every little step you take towards getting healthy, counts. They all add together to contribute to your state of health, today. So every little step you take in the right direction, matters. Don’t get discouraged if things don’t move right away, just keep trying.

Share with friends:

MTHFR and Homocysteine By The Numbers

These past few weeks we’ve gone over some general information about MTHFR and homocysteine, the link between methionine and homocysteine, and the new information about MTHFR, homocysteine, and Covid-19. What we haven’t talked about is Homocysteine testing and parameters – what is normal, what isn’t, and what is considered normal but maybe shouldn’t be.

Testing Homocysteine

Homocysteine tests are simple blood tests that can be ordered by your doctor. It must be performed fasting for accurate results. Any protein you eat before your test can skew the numbers because methionine in your food may cause a temporary rise in homocysteine. The best way to ensure a blood test is fasting is to schedule your blood test early in the day before you have eaten anything. 8 – 12 hours of fasting (like you would get overnight) is best for the most accurate results.

“Normal” Levels

The current medical standard in the U.S. is a normal range from 5 – 15 umol/L (that is micro mols/Litre). Anything above 15 micro mols/L is considered high, or hyperhomocysteinemia. There is a growing body of evidence that the normal level should be adjusted:

  • A study published in the New England Journal of Medicine shows that carotid artery thickening and stenosis risk begins to increase for men by 9.2 umol/L (although the risk for women seems to remain stable until 11.4 umol/L). Both of these are significantly lower than the 15 umol/L that is considered normal.
    • Risk increases at 9.2 umol/L
  • A meta-analysis published in the Journal of the American Medical Association shows that a 3 umol/L decrease in homocysteine leads to an 11% lower risk of ischemic heart disease and a 19% lower risk of stroke.
  • A strong linear relationship exists between homocysteine levels and death in patients with coronary disease. The lowest risk group has homocysteine below 9 umol/L and the risk increases from there both within what is considered the normal level and outside of it.
    • Homocysteine <9 umol/L = 3.4% risk of death
    • Homocysteine 9 umol/L – 14.9 umol/L = 8.6% risk of death
    • Homocysteine >15 umol/L = 24.7% risk of death.
    • Risk increases at 9 umol/L
  • The study we discussed last week dealing with homocysteine levels as a predictive marker for worse outcomes with Covid-19 also showed an increased risk for pathological lung changes on CT at 8 umpl/L
    • Risk increases at 10.58 umol/L

If The “Normal” Levels aren’t Ideal, What Is?

All of the risks for negative health outcomes seems to be lowest around the 6 – 8 umol/L mark, so we’re going to call that “Optimal.” This is an estimation based on the research that we talked about above. Joe Pizzorno (a legend in the natural wellness community), estimates the ideal range to be 5.0 to 7.0. Ben Lynch, the epigenetic expert, estimates ideal to be between 6 to 9 umol/L.

If Homocysteine Is So Bad, Why Aren’t We Aiming for Zero?

Too much homocysteine is bad for sure, and with MTHFR and homocysteine that is the direction we usually trend, but remember that homocysteine is absolutely essential. If your homocysteine is too low (hypohomocysteinemia), then there are also health consequences. Without homocysteine you can’t make glutathione, which is one of your main defenses against oxidative stress. Without glutathione, things would go sideways pretty quickly.

Homocysteine is also the precursor for something called alpha-ketobutyrate, which is a vital ingredient in the process that makes cellular energy. Very few studies are done about low homocysteine levels (I mean VERY few. I can count them on two hands). By far the most interesting one shows a link between low homocysteine and peripheral neuropathy. It states that fully 41% of people with low homocysteine have peripheral neuropathy, which is hugely significant.

In my opinion, this implies that the lack of glutathione and consequent difficulty with free radicals is leading to higher levels of inflammation and nerve damage. Ben Lynch put forward a similar theory on his website here, and Joe Pizzorno, here.

I wouldn’t be surprised to see a link between low homocysteine and chronic fatigue, as well, although the research has never been done.

The bottom line is that we need homocysteine, but too much of it becomes a big problem. Aim for 6 – 8ish micro mols/L. Next week we’ll talk about ways to lower your homocysteine levels if they’re too high.

Has your homocysteine ever tested too low? I”d love to hear your comments here, or in Genetic Rockstars, our amazing MTHFR community.

Share with friends: