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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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.

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