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MTHFR Gene Mutation: Symptoms & Treatment

Written by Dr. Michael Ruscio, DC on April 22, 2025

Written by Dr. Michael Ruscio, DC on April 22, 2025 — Reviewed by Kellie Blake

• What Is MTHFR?|
• MTHFR Gene Mutations|
• MTHFR Testing|
• Impact on Pregnancy|
• Symptoms|
• Gut Health and Treatment|

An MTHFR gene mutation might seem to explain your symptoms, from chronic fatigue and pain to brain fog, anxiety, major depression, and hormonal imbalances. But a closer look at the research shows that the health impacts of these common gene variants may actually be quite minimal.

The symptoms that have been associated with MTHFR gene variations are more likely to be caused by gut imbalances and inflammation. This is good news because these imbalances and their treatments are better understood. 

In this article, I’ll break down the different MTHFR variants, other possible causes of symptoms like fatigue, pain, brain fog, digestive symptoms, mood disorders, and hormonal imbalances, and how to treat them.

What Is MTHFR? 

MTHFR (short for methylene-tetra-hydro-folate reductase) is both a gene and an enzyme. When people talk about MTHFR, they are generally referring to the gene that tells the body how to make the enzyme. The MTHFR enzyme plays a role in various functions in the body, which we’ll cover in more detail below.

MTHFR Gene Mutations (Variants)

Many people have slight changes, or variants, in their MTHFR gene. Some have linked these changes to conditions like bipolar disorder, schizophrenia, chronic pain, heart disease, and autism. However, the science on this is still unclear.

The two most common variants of MTHFR are 1:

• C677T – Found in about 38% of people
  
• A1298C – Found in about 40% of people

You can have one, both, or neither of these variants in your MTHFR gene. 

Even though these are sometimes called “mutations,” experts say “polymorphism” is a better word because these changes aren’t necessarily bad. It’s similar to how some people have brown eyes and others have blue—it’s just a difference 2.

True MTHFR mutations (the kind that cause serious health problems) are very rare. These can lead to seizures, intellectual disabilities, and, in some cases, pregnancy complications like miscarriage or birth defects 3.

But common MTHFR variants are actually pretty normal. In fact, 30–60% of people have at least one of these variants 4, and only about 15% of the population has an MTHFR gene with no changes at all 5. So, despite what you might hear online, MTHFR variants are more common than not!

MTHFR Gene Mutation Testing: Does It Work?

With the advances in genetic understanding in recent years, testing for variants in genes (like with a MTHFR test) for health optimization purposes is popular. But research suggests that the results are generally not useful.

• A review of studies found that testing for MTHFR gene variants has little to no useful medical benefit 6. 
• The American Heart Association also concluded that there was no good reason to regularly test for MTHFR polymorphisms in any group of patients 4.
• Other research reviews have found that, in most cases, consumer genetic test results don’t accurately reflect a person’s true risk of developing a disease 7 8. 

In other words, genetic testing results aren’t very useful and can distract you from what’s really causing your symptoms and the types of treatment that can help you. 

Gene testing can also be very disempowering. Why focus on one small thing you can’t control when there are clear and proven approaches for taking charge of your health? 

How Does MTHFR Impact Pregnancy?

The MTHFR gene helps the body create an enzyme that converts folic acid (from food and supplements) into methylfolate, the active form of folate your body uses. Folate is essential for many processes, including hormonal balance, brain function, and nutrient metabolism.

Some people worry that MTHFR gene variants slow down this conversion process and increase health risks, particularly during pregnancy. But what does the research actually say?

While some studies have suggested that certain MTHFR gene variants could increase pregnancy risks, the overall scientific evidence does not support this. In fact, research shows that while the MTHFR enzyme’s activity may be slightly reduced in some people, this reduction is not significant enough to cause major health problems for you or your baby.

Should I Avoid Folic Acid While Pregnant? 

Another common misconception is that pregnant people with an MTHFR gene variant should avoid folic acid supplementation and opt for a more costly form of folate supplement called methylfolate or for a vitamin B complex with methylfolate instead. 

However, the effects and benefits of folic acid and methylfolate supplements are similar, and there don’t seem to be any risks associated with taking the more affordable folic acid 9. The same goes for non-pregnant people with a MTHFR polymorphism. Notable research has shown:

• People with common MTHFR polymorphisms may have a 30% lower risk of stroke when taking standard folic acid supplements. Standard folic acid supplementation is both safe and effective for those with MTHFR polymorphisms 10.
• Folic acid is often recommended for women of childbearing age to help prevent neural tube defects in their children. Research shows that prenatal folic acid supplements benefit mothers and their babies, regardless of MTHFR gene status 9.

If you’re pregnant or trying to conceive, having an MTHFR variant is not a cause for alarm. The best thing you can do is:

• Take a prenatal vitamin with folic acid.
• Eat a balanced diet with folate-rich foods (leafy greens, beans, citrus fruits).
• Follow your doctor’s recommendations.

The good news? You don’t need to make drastic changes based on your MTHFR status. The research simply doesn’t support the idea that these variants have a major impact on pregnancy when you’re getting enough folate.

Conditions Linked to MTHFR Mutations

Some supporters of the MTHFR theory claim that it increases the risk of cardiovascular disease and related conditions like blood clots, stroke, high blood pressure, and thrombosis (blood clotting within a blood vessel). 

Their concern is based on the idea that MTHFR gene variants may lead to lower levels of folate (vitamin B9) and vitamin B12, and higher levels of homocysteine—factors that have all been linked to heart disease.

A study in China found that people with a common MTHFR polymorphism had higher levels of homocysteine and lower folate and B12, but other factors likely also played a role in their heart disease risk 10.

Does an MTHFR Mutation Increase My Risk for Heart Disease?

Many risk factors can contribute to elevated homocysteine levels. Broadly, a healthy diet, lifestyle, and gut are essential to heart health and preventing cardiovascular disease. 

In particular, eating an anti-inflammatory diet rich in healthy fats, proteins, and nutrient-dense fruits and vegetables, getting enough sleep, and exercising regularly can all reduce your risk of heart disease. 

Gut microbial imbalances have been linked to heart disease 11. Probiotics can help by changing gut bacteria in ways that reduce homocysteine levels and boost B vitamin levels 12.

It’s important to focus on the basics of good health because worrying too much about a single gene (which you can’t control) may end up distracting you from the diet and lifestyle choices that actually help keep your heart healthy.

If you’re worried about your folate, vitamin B12, or homocysteine levels for any reason, simple blood tests can determine your actual status 13 14.

Symptoms Linked To MTHFR Mutations

Beyond heart disease, several different kinds of symptoms have been attributed to MTHFR gene mutations, including fatigue, chronic pain, brain fog, depression, anxiety, estrogen dominance, and headaches. 

These are common symptoms that we see and treat daily in our clinic. Although the symptoms themselves are very real and troubling for our clients, chances are, they’re not caused by MTHFR gene polymorphisms. Generally, these symptoms are signs of systemic inflammation and imbalances in the gut.

Let’s take a closer look at some of these symptoms, explore what probably causes them, and discuss how to treat them.

Fatigue

Gut imbalances often go well beyond digestive distress, and fatigue is a common example. 

There’s a strong connection between fatigue and several different gut conditions, including irritable bowel syndrome (IBS), increased intestinal permeability (leaky gut), gut infections, and non-celiac gluten sensitivity. For instance, studies have shown that:

• Fatigue is one of the most common symptoms of IBS 15, and more than 50% of IBS patients may report it 16. 
• Tiredness is one of the most common symptoms of non-celiac gluten sensitivity, and 64% of patients may report it 17.
• Fatigue may be linked to imbalances in the gut microbiome 18.
• Fatigue is a common symptom of a leaky gut 19. 

Healing the gut may help to resolve chronic fatigue or low energy. Research has shown:

• Treating a leaky gut may reduce fatigue in people with chronic fatigue syndrome 19. 
• Following a low FODMAP diet, which is commonly recommended for people with small intestinal bacterial overgrowth (SIBO) and IBS, can improve fatigue and digestive symptoms 20. 
• Probiotics may help fatigue by balancing bacteria in the gut, reducing inflammation, and healing a leaky gut 21. 

Chronic Pain 

Chronic joint and muscle pain are often related to gut imbalances. Research has shown:

• Gut imbalances have been linked to joint pain and inflammation 22. 
• Joint pain is a common symptom of IBS 23.
• Muscle and joint pain are common symptoms of non-celiac gluten sensitivity and may affect 31% of patients 17. 
• 48% of fibromyalgia patients may have IBS 23. 

Dietary strategies and therapies that target the gut can improve joint and muscle pain in people with gastrointestinal disorders and those with chronic pain disorders. Evidence suggests that:

• Reducing dietary sugar, which contributes to intestinal inflammation and imbalances, can improve muscle and joint pain in people with IBS 24. 
• An elemental diet (a therapy that reduces gut dysbiosis) can improve pain and joint stiffness in people with rheumatoid arthritis 25. 
• Following a low FODMAP diet, which is often used to starve bacterial overgrowths in the gut, may reduce pain in people with fibromyalgia 26.

Brain Fog

Brain fog, or difficulty thinking clearly, concentrating, or remembering, is commonly reported among people with gut imbalances. According to research:

• Gut dysbiosis, or imbalances in the gut microbiome, can affect brain function 27.
• People with IBS commonly report feeling both fatigued and less able to handle stress 15.
• Brain fog is a common symptom of celiac disease and non-celiac gluten sensitivity 28 29. 

Diets and treatments that address inflammation and gut imbalances may help improve cognitive function and symptoms like brain fog. Studies suggest:

• An anti-inflammatory diet may help reduce brain inflammation and a leaky gut, which may improve brain fog 30.
• Probiotics can improve cognitive function in healthy older adults and in people with fibromyalgia or Alzheimer’s disease 31 32 33.

Bipolar, Major Depression, and Anxiety 

Anxiety, depression, and other mental health conditions are often connected to inflammation and gut health. According to studies:

• Depression and anxiety are common in people with digestive disorders like IBS and non-celiac gluten sensitivity 15 17.
• A leaky gut may contribute to depression and anxiety 34. 

Healing the gut with the help of probiotics and diet can help treat depression and anxiety. Studies have found:

• Anxiety may improve in more than 50% of sufferers who use therapies like probiotics and diet, which support a balanced gut microbiome 35. 
• Probiotics can improve mild to moderate depression 36. 
• Following a low FODMAP diet may reduce anxiety and depression, and boost overall happiness in people with IBS 37. 

A meta-analysis (study of studies) found a connection (not cause-and-effect) between certain MTHFR gene polymorphisms (C677T and A1298C) and conditions like ADHD, bipolar disorder, and schizophrenia 38. Although these findings are certainly interesting and warrant further research, they have limitations, including:

• Small sample sizes that make it hard to draw strong conclusions
• Unaccounted factors like ethnicity, control group differences, diagnostic criteria, and socioeconomic status
• The unknown effects of different types of mental disorders, gene interactions, and epigenetics

Given the limited evidence on causation and the fact that you can’t change your genes, it’s worth leaning into what you can control, like improving your gut health, which can significantly impact mood and cognition.

Estrogen Dominance 

Hormonal imbalances, especially estrogen dominance, are sometimes attributed to MTHFR gene polymorphisms. However, research does not strongly support this connection. 

Instead, things like how you live and eat, exposure to pollution, your genes, problems with gut health, and being overweight are likely to increase the risk of hormone imbalances in women. 

Research shows that estrogen dominance and its symptoms—irregular periods, mood swings, heavy or painful periods, bloating—and conditions like PCOS (polycystic ovary syndrome) may be linked to imbalances in the gut microbiome, which can interfere with estrogen levels 39. 

Although research is limited, some evidence suggests that probiotics may help to balance estrogen and other hormones by improving gut health and reducing inflammation 40. 

Migraines and Headaches

More likely than stemming from an MTHFR polymorphism, migraines and headaches are common symptoms of gut issues like IBS and non-celiac gluten sensitivity 17 41. 

Though research on treating migraines in IBS patients is very limited, a case study found that a low FODMAP diet has the potential to help 42. And a gluten-free diet may improve migraine symptoms in people with non-celiac gluten sensitivity 43. 

Treatment for an MTHFR Mutation

When it comes to your health, it’s very important to take a step back from the minutia and focus on the big picture. 

Research demonstrates over and over the importance of health fundamentals. Eating well, living a healthy lifestyle, and keeping your gut in good shape are some of the key ways to improve your overall health and ease the symptoms linked to MTHFR gene mutations. 

Key lifestyle factors, like eating an anti-inflammatory diet, moving your body regularly, and getting enough sleep, can lead to clear and meaningful health and wellness benefits, regardless of your genetic profile. 

Treatments that target the gut, including probiotics, can help resolve many of the imbalances and symptoms associated with MTHFR gene variants.

To learn more about how to heal your gut and resolve your MTHFR mutation-related symptoms, check out my book, Healthy Gut, Healthy You. 

For more personalized help sorting out the true cause of your symptoms and which medical advice makes the most sense for you, our virtual clinic is accepting new clients.

The Ruscio Institute has developed a range of high-quality formulations to help our clients and audience. If you’re interested in learning more about these products, please click here. Note that there are many other options available, and we encourage you to research which products may be right for you. The information on DrRuscio.com is for educational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.