MTHFR, Genetics, and Stress: A Recipe for Anxiety and Depression - Doctor Doni (2024)

Dr. Doni explores the relationship between genetic mutations, MTHFR, mood and stress, and explains why a whole body approach is the best way to feeling better.

Part 5 of Dr. Doni’s Series on How Genetic Mutations Affect Your Health

Almost every patient I see has some history of anxiety, depression, PMS, PMDD (pre-menstrual dysphoric disorder), or other mood-related health issue. And when you read about my health story (which you can find in my book, The Stress Remedy), you’ll find that I have too. To me, as a naturopathic doctor, mood is inextricably connected to your body as a whole; I know this on a scientific level simply because hormones, cytokines, and neurotransmitters travel throughout our bodies, including to the brain. How could mood and physical health be separate? And yet, all too often in the current medical model and culture, mental health issues are looked at separately from physical health issues.

In actuality, mood is affected by many things happening inside your body. Changing blood sugar levels, menstrual hormone fluctuations, lack of sleep, nutrient deficiencies, pain, low thyroid function, decreased or increased cortisol at the wrong time of day, digestive issues including leaky gut, neurotransmitter imbalances, and “simple” stress all have the ability to disrupt even the most stable mood. I call them “mood disruptors.” Add genetic mutations (such as MTHFR) that can influence mood to the list and it’s amazing that we’re ever in a good mood!

You’ve seen me write a lot about how to manage many of these of mood disruptors, but not so much about the influence of genetic mutations. So in today’s article, I want to bring it all together by delving deeper into understanding how genetic mutations can affect our mood, how they relate to the other mood disruptors, and what you can do about it.

This article comes mid-way through a series on How Genetic Mutations Affect Your Health. The first four articles in the series describe genetic mutations (SNPs), how to test for them, and the SNPs that affect the methylation cycle.

The list of mood disruptors can be quite overwhelming to sort out on your own, especially because most practitioners don’t see or address the connection between your body and your mind. As a result, I hear from patients every day who have seen practitioner after practitioner without feeling any better.

In fact there are millions of people with mood-related health issues in the United States and around the world, most of whom have not had help to address the underlying mood disruptors. One study found that, in 2011, one in five men and one in four women in the U.S. were taking a psychiatric medication daily, a number that had doubled in the previous decade. Many of those patients also experienced physical symptoms and yet often felt dismissed by medical providers, being told that their health concerns were “all in their head” (click here to read the report in full).

All of this, plus my experience helping patients with a “whole body” naturopathic perspective for over 15 years, has inspired me to get the word out about how we can address mood by understanding the body and what it needs. And what I’ve consistently found after reviewing the research is that when we look at mood issues from the perspective of stress, we can unravel much of the mystery.

There are literally thousands of articles linking mental health issues to stress and the imbalanced hormones, cytokines, and neurotransmitter levels that result. That is what I wrote about in an article titled Anxiety and Depression: It All Starts with Stress (2009) and in my book, The Stress Remedy (2013). Stress, whether emotional or physical, chronic or acute, big or small, leads to a what I call the 3 Problem Networks of Stress: adrenal distress, blood sugar imbalances, and leaky gut.

Now, as I describe in The Stress Remedy, a growing numbers of studies make a connection not just from the brain to the gut, but from the gut back to the brain. What?! That’s right… imbalance in healthy gut bacteria (dysbiosis) and leaky gut can trigger inflammatory messages that travel to your brain (you can read more about this here). They also disrupt levels of neurotransmitters that are produced in your gut and affect your mood. I’m excited to be presenting this whole topic to my colleagues at the Pennsylvania Association of Naturopathic Physicians Annual Conference in June.

Understanding how stress affects our bodies also helps when looking at how genetic mutations influence mood. Studies show this is because genetic mutations only have the opportunity to affect our health and mood when we are under stress—a scientific phenomenon referred to as epigenetics—which also means that we have the ability to change the way our genetics influence our mood by optimizing our stress.

For example, one study found that exposure to stress during childhood increases risk of depression by increasing inflammatory responses that affect the nervous system. Meanwhile, other studies show that stress reduction techniques help to improve depression. So one clear way to address mood issues from a whole-body approach is to optimize our stress response and implement stress remedies, which you can read all about in my 99 cent ebook, Stress Remedies.


Methylenetetrahydrofolate reductase (MTHFR) converts folic acid (which is synthetic) to methylfolate (also known as 5MTHF or active folate). Methylfolate then goes on to power the methylation cycle, leading to methionine and the metabolic processes that create and break down our neurotransmitters such as serotonin, dopamine, and norepinephrine (amongst other things which you can read about in my article all about MTHFR). If you have this SNP, it means that you are more likely to have an imbalance of neurotransmitter levels, which can affect mood, especially when you are stressed.

The solution is to avoid folic acid and instead to take some amount (the right amount for you) of methylfolate along with nutrients to support the methylation cycle. Before you jump into taking methylfolate, however, it is important to take into account whether you have any of the other SNPs that can affect mood, and if you do, then address them prior to taking methylfolate.


Catechol-O-methyltransferase (COMT) is an enzyme that breaks down catecholamines, which include what we think of as adrenaline (epinephrine and norepinephrine). When we are under stress, adrenaline levels rise—causing fear, anxiety, panic, and a racing heart. A person with COMT mutations will be less able to remove adrenaline from their body and more likely to experience these stressful feelings. Dopamine is also a catecholamine that is broken down by COMT, and if that function is decreased, elevated dopamine levels can result, affecting mood as well as focus. One starting step is to decrease the amount of catechols you get in your diet, such as from potatoes, green tea, and coffee. Next is to support COMT function with magnesium bisglycinate and vitamin B6 (the active form is P5P).


Monoamine oxidases (MAO types A and B) have the role of removing an amine from monoamines—such as serotonin, melatonin, dopamine, and adrenaline—leading to the production of ammonia and aldehyde, which must be further detoxified and can cause fatigue, brain fog, and pain. So if you have this mutation and this process either doesn’t happen or is disrupted in some way, you may have increased or decreased levels of neurotransmitters and the metabolites that can increased toxicity in your body. MAO mutations have been shown to be associated with anxiety, depression, and other mood issues. If you have this SNP, you could start by decreasing the amount tyramines in your diet, such as from aged cheese, pickles, and/or other fermented or aged foods.


Glutamic acid decarboxylase (GAD) turns glutamate into GABA. Glutamate is stimulatory to the nervous system and GABA and calming, so the balance of the two greatly influences the way you feel. Someone with GAD SNPs is more likely to feel anxious. Magnesium (bisglycinate) and vitamin B6 (P5P) support the function of GAD and would be a good place to start if you have GAD SNPs.

First of all, if you’d like to find out if you have any of these genetic mutations (and others), then be sure to read the earlier article in this series that talks about testing for genetic mutations.

Then, once you have your genetic report and have identified which mutations you have, you’ll want to meet with a practitioner who is trained in this area and can help you with follow up tests to give you a clearer sense of how the mutations may be affecting your health. You may need to do a salivary cortisol and urinary neurotransmitter panel—so we can see exactly how stress has affected your stress hormones and neurological messengers.

You may also need to do an organic acids panel to see the metabolites that affect mood, and nutrient levels to identify nutrient (cofactor) deficiencies. Then, if you haven’t already, completing a food sensitivity panel to determine which foods put stress on your body and the degree to which leaky gut is involved is imperative. A stool panel may also be necessary to identify dysbiosis (imbalanced gut bacteria).

As all of this information comes in, you and your practitioner will be able to create a strategic plan to address each of these areas in an integrated way, keeping in mind that they all influence each other.

An example plan looks like this:

  • Phase 1: Review your case and determine which further tests are needed.
  • Phase 2: Review supplements* and make sure you have the best foundational nutrients.
  • Phase 3: Integrate leaky gut healing support—diet changes and supplements.
  • Phase 4: Add in supplements to balance neurotransmitters and cortisol levels.
  • Phase 5: Address dysbiosis and/or other infections if necessary.
  • Phase 6: Identify and address toxic exposures and/or blood sugar imbalances.
  • Phase 7: Support the methylation cycle and genetic SNPs.

So you see that addressing mood issues is mostly about addressing the whole of your body. It’s not about a single pill. And definitely not a miracle pill. It is about looking at your body as a whole integrated system and supporting every part of that system to work well again. It takes time, diligence, consistency, and determination. Not perfection—but an attitude of curiosity and acceptance.

When people ask me how I can help them I say, “Let’s sit down and look at all the data together. Then let’s make a plan that is specific to you. We can start that process during an initial consultation – what I call a Comprehensive Health Breakthrough Session—and then we can decide whether a program or package makes sense, in terms of getting everything you need at a lower cost and with access to discounts on supplements.”

I created a package specifically for looking at your genetic mutations and how they may be affecting your health—it’s called the Genetic Profiling Solutions Package. It includes a plan just as I have laid it out above (with testing) to learn about your cortisol, neurotransmitters, and nutrient levels, as well as a phased approach to implementing steps to help with your mood and any other health issues. If you would like to make appointment with me to discuss the best approach for you, you can do so by clicking here.

The message I want you to take away, especially if you have been struggling with mood-related issues, is that it is possible to feel better. It is not something that happens all at once, and you’ll need to continue to take ongoing steps to optimize your mood based on your current circ*mstances and stress levels. But it is possible, with the right kind of professional support, to address the various mood disruptors and genetic mutations that are affecting you.

If you’d like to start learning more, my book, The Stress Remedy, will walk you through the information step-by-step with case studies to illustrate. It includes a complete health questionnaire and a 3-week menu plan with recipes.

I’d love to hear your thoughts on how to address mood from a perspective of stress. Please share below in the comments box.

–Dr Doni
17th April 2015

*Please keep in mind that any and all supplements—nutrients, herbs, enzymes, or other—should be used with caution. My recommendation is that you seek the care of a naturopathic doctor (with a doctorate degree from a federally-accredited program) and that you have a primary care physician or practitioner whom you can contact to help you with individual dosing and protocols. If you ever experience negative symptoms after taking a product, stop taking it immediately and contact your doctor right away.

MTHFR, Genetics, and Stress: A Recipe for Anxiety and Depression - Doctor Doni (2024)


How do you treat MTHFR anxiety? ›

B-vitamins show promise in treating depression and anxiety, especially if it's associated with MTHFR mutations. Studies show that appropriate levels of methylcobalamin (vitamin B12), methylfolate and SAMe help with mental health by normalizing MTHFR conversion activities in our bodies4.

Can the MTHFR gene cause depression? ›

Depression can be influenced by your unique genetic code. Your MTHFR gene may be particularly implicated in negative health outcomes. Genetic testing can help you and your doctor get to the root causes of your depression, and lifestyle and dietary interventions can help you feel whole again.

What is the genetic mutation for anxiety? ›

MTHFR can cause many mental health problems that are strongly associated with anxiety, these include: Depression. Generalised Anxiety disorder. Low self esteem.

Can you take methylfolate for anxiety? ›

In my professional practice, I use methylfolate in addition to prescribed antidepressants. I find that some patients feel a dramatic benefit within days of starting methylfolate. Others don't feel much but I see a reduction in their depression and anxiety scores in my monthly measurements.

What is the best antidepressant for MTHFR? ›

If a genetic test is administered and their medical practitioner is able to determine a mutation with their MTHFR gene, they can prescribe L-methylfolate along with an SSRI and enable significantly better outcomes for their patients.

What are the mental health symptoms of MTHFR? ›

Key points. Mental health issues associated with a MTHFR mutation include depression, bipolar disorder, schizophrenia, and ADHD.

Why don t doctors believe in MTHFR? ›

There is a large contrast between “single gene” conditions, like cystic fibrosis, and genes that may affect health in concert with many others. MTHFR is the latter, we can't pin a single health condition on MTHFR polymorphisms, standing alone, period. This means having MTHFR symptoms is impossible.

What makes MTHFR worse? ›

Those with MTHFR genetic variations are more likely to have an imbalance of neurotransmitter levels, which can affect mood and irritability, especially when stressed. In fact, high levels of stress can exacerbate MTHFR mutation symptoms.

What psychiatric disorder is associated with MTHFR mutations? ›

This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.

How do you fix genetic anxiety? ›

  1. getting more exercise.
  2. reducing your intake of caffeine.
  3. avoiding recreational drugs and alcohol.
  4. eating a balanced diet.
  5. getting adequate sleep.
  6. using relaxation techniques, such as yoga and meditation.
  7. managing your time to reduce stress.
  8. socializing and talking to supportive people about your anxiety.
Jun 27, 2019

How can you prove if anxiety is genetic? ›

Anxiety disorders can run in families, suggesting a familial or genetic component. You're more likely to struggle with anxiety if a close relative also struggles with it. In addition, the presence of anxiety disorders among relatives can indicate a shared genetic vulnerability to the condition.

Is anxiety inherited from mother or father? ›

Children with generalized anxiety disorder are 3.5 times more likely to have a mother with generalized anxiety disorder. Children with social anxiety disorder are almost 3 times more likely to have a father with anxiety disorder.

What supplements should you avoid with MTHFR? ›

Folic acid is the synthetic form of folate that cannot be used by those with a MTHFR defect and which can be very toxic. avoid any supplements with folic acid and only take L-MTHF forms, which are the methylated forms that my body can use. Also take a methyl-B12 which is supposed to help the body use L-MTHF.

Is MTHFR a big deal? ›

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that breaks down the amino acid hom*ocysteine. If the MTHFR gene that codes for this enzyme mutates, it may contribute to a variety of health conditions ranging from depression to some cancers.

Can lack of folate cause anxiety? ›

Low Folate levels and accumulation of these byproducts have been shown to contribute to symptoms of anxiety, depression, and other mood disorders.

What medications should be avoided with MTHFR? ›

Drugs to avoid with MTHFR Mutation
  • Antacids (depletes B12)
  • Proton Pump Inhibitors (depletes B12)
  • Cholestyramine (depletes B12 & folate)
  • Cholestipol (depletes B12 & folate)
  • Methotrexate (inhibits DHFR: Folate->THF)
  • Nitrous Oxide (Inhibits MTR – Methionine Synthase)
Apr 13, 2017

Can MTHFR cause anxiety? ›

MTHFR mutations, for which at least 24 known genetic polymorphisms have been identified, are associated with metabolic dysfunction. They play a suspected role in several physiologic symptoms—including anxiety. The most common MTHFR mutation is the MTHFR C677T mutation.

What medication is used for MTHFR? ›

MTHFR Polymorphism and Antifolates

The antifolate drugs methotrexate (MTX), pernetrexed, edatrexate, and lometrexol are structural folate analogues that target different enzymes of the folate cycle and/or purine or pyrimidine synthesis.

Does Sam E work for anxiety? ›

People most commonly take SAMe for depression and osteoarthritis. It is also used for anxiety, liver disease, fibromyalgia, schizophrenia, and many other conditions, but there is no good scientific evidence to support these uses.

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