MTHFR Mutation Symptoms, Diagnoses & Natural Remedies

A MTHFR mutation is a problem associated with poor methylation and enzyme production. MTHFR gene mutation issues affect every person differently, sometimes contributing to hardly any noticeable symptoms at all, while other times leading to serious, long-term health problems.

Although the exact prevalence rate is still up for debate, it’s believed that up to 30 percent to 50 percent of all people might carry a mutation in the MTHFR gene, some estimates even going all the way up to 70 percent, which is inherited and passed down from parent to child. Around 14 percent to 20 percent of the population might have a more severe MTHFR mutation that impacts overall health more drastically.

The MTHFR gene mutation was discovered during the completion of the Human Genome Project. Researchers realized that people with this type of inherited MTHFR mutation tended to develop certain diseases, including ADHD, Alzheimer’s, atherosclerosis, autoimmune disorders and autism, more often than those without the mutation.

There is still a lot to learn about what a MTHFR gene mutation means for people who carry it and go on to pass it along to their children, but it’s believed to affect people in different ways.

To date, there have been dozens of different health conditions tied to MTHFR mutations, although just because someone inherits a MTHFR gene mutation doesn’t mean that person will wind up experiencing any problems.

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What is a MTHFR gene mutation?

According to the Genetics Home Reference Library, MTHFR is a gene that provides the body with instructions for making a certain enzyme called methylenetetrahydrofolate reductase. In fact, “MTHFR” is the shortened name for this enzyme.

There are two main MTHFR mutations that researchers focus on most often. These mutations are often called “polymorphisms” and affect genes referred to as MTHFR C677T and MTHFR A1298C.

Mutations can occur on different locations of these genes and be inherited from only one or both parents. Having one mutated allele is associated with increased risk of certain health problems, but having two increases the risk much more.

An MTHFR gene mutation can change the way some people metabolize and convert important nutrients from their diets into active vitamins, minerals and proteins. Genetic mutations can also alter neurotransmitter and hormone levels.

In some cases, although not all, changes in how this enzyme works can affect health parameters, including cholesterol levels, brain function, digestion, endocrine functions and more.

Variants

As mentioned, two of the most researched MTHFR gene mutations are called C677T and A1298C. These are single nucleotide polymorphisms, which means that one building block of DNA is replaced by another.

• C677T variant: In this mutation, cytosine (C) is replaced by thymine (T) at position 677 of the gene. People who inherit two copies (homozygous) of the T allele may have reduced MTHFR enzyme activity, which can result in higher homocysteine levels if their folate intakes are low.
• A1298C variant: This occurs when adenine (A) is replaced by cytosine (C) at position 1298. By itself, A1298C generally has less effect on enzyme activity than C677T, but it can still contribute to methylation issues, especially if someone carries one copy of each variant (compound heterozygous).

Most people with these variants do not experience severe health problems, especially if they consume adequate folate, vitamin B12 and other methylation-supporting nutrients. The impact of an MTHFR gene mutation usually depends on lifestyle, diet and other genetic factors.

MTHFR mutation symptoms

Although researchers still aren’t entirely sure which diseases and disorders an MTHRF mutation might contribute to most, evidence exists that the following health problems (and more) are tied to one of two primary forms of genetic MTHFR mutation:

• Autism and other childhood learning developmental problems
• ADHD
• Down syndrome
• Depression and anxiety
• Spina bifida
• Schizophrenia
• Bipolar disorder
• Autoimmune disorders and thyroid disorders
• Addictions (alcohol and drug dependence for example)
• Chronic pain disorders
• Migraines
• Heart problems, including low HDL “good” cholesterol levels and high homocysteine levels
• Hormonal problems and fertility problems, including miscarriages and PCOS
• Pulmonary embolisms
• Fibromyalgia
• Diabetes
• Chronic fatigue syndrome
• Parkinson’s disease, other tremor disorders and Alzheimer’s disease
• Strokes
• Digestive problems, including irritable bowel syndrome
• Problems during pregnancy, including preeclampsia and postpartum depression

The severity and type of symptoms that someone experiences depends on the variant of the MTHFR gene mutation the person has, along with how much the ability to carry out methylation and make MTHFR enzymes is impacted.

Some people produce up to 70 percent to 90 percent fewer enzymes than those without a MTHFR mutation. Others experience much less drastic drops in enzyme levels, around 10 percent to 30 percent.

Causes and risk factors

The primary reason that MTHFR mutations cause health problems is due to disturbing the normal process of methylation.

To understand why a MTHFR gene mutation can raise your risk for common disorders, it helps to first understand the important roles that methylenetetrahydrofolate reductase normally plays. MTHFR normally:

• Facilitates the process called methylation, which is a metabolic process that switches genes on and off and repairs DNA. Methylation also affects nutrient conversions through enzyme interactions.
• Forms proteins by converting amino acids (often called “the building blocks of proteins,” which we mostly obtain from foods).
• Converts the amino acid called homocysteine into another amino acid called methionine. This helps keep cholesterol levels balanced and is important for cardiovascular health. Elevated homocysteine levels put someone at a greater risk for heart attacks, strokes and other problems.
• Carries out chemical reactions that help the body process the vitamin folate (also called vitamin B9). This is done by converting one form of the methylenetetrahydrofolate molecule into another active form called 5-methyltetrahydrofolate (or 5-MTFH for short). Folate/vitamin B9 is required for numerous critical bodily functions, so the inability for the body to make and use enough (or a folate deficiency) can affect everything from cognitive health to digestion.
• Methylation is also tied to natural detoxification because it helps eliminate heavy metals and toxins through the gastrointestinal tract in a timely manner.
• Methylation also helps with the production of various neurotransmitters and hormones, including serotonin. Deficiencies in these neurotransmitters can affect things like your mood, motivation, sleep, sex drive, appetite and digestive functions. Abnormal levels of neurotransmitters are tied to ADHD, depression, anxiety, IBS and insomnia.
• In order for methylation to take place, the body requires the presence of a certain active amino acid called SAM-e, which helps regulate more than 200 different enzyme interactions. Without it, methylation stops.

Whether you carry the MTHFR C677T or MTHFR A1298C mutation determines if you’re more likely to suffer from certain diseases than others.

• MTHFR C677T mutations are tied to cardiovascular problems, elevated homocysteine, stroke, migraines, miscarriages and neural tube defects. Some studies suggest that people with two C677T gene mutations have about a 16 percent higher chance of developing coronary heart disease compared to people without these mutations.
• MTHFR A1298C mutations are tied to higher levels of fibromyalgia, IBS, fatigue, chronic pain, schizophrenia and mood-related problems. This is especially true if you’ve inherited the mutation from both parents or have both forms of MTHFR mutations.

Someone can either have a heterozygous MTHFR mutation (from one parent) or a homozygous MTHFR gene mutation (from both parents). Those with homozygous mutations tend to have more severe symptoms and health problems due to having lower methylation and enzyme production.

Testing and diagnosing

Many people have no idea that they carry a MTHFR gene mutation that contributes to their symptoms. How can you know if you’re carrying one of several common MTHFR mutations?

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If you suspect you might be affected by an MTHFR mutation, consider having a genetic test performed, which is a simple blood test that can confirm your suspicions. This type of test isn’t routinely ordered by doctors but might be recommended if someone has high homocysteine levels or a family history of heart complications.

Other tests that can help confirm a MTHFR gene mutation include heavy metal tests, urine tests, homocysteine level tests, folic acid tests, leaky gut test and hormone level testing.

Because it’s a problem related to an inherited gene, there is no way to “cure” an MTHFR mutation. However, certain lifestyle changes and natural treatments can help manage symptoms and make complications less likely.

Natural treatments for methylation problems depend on your specific symptoms and condition. The steps below can help reduce symptoms caused by disorders related to MTHFR mutations.

MTHFR gene mutation and pregnancy

Because folate metabolism is crucial during pregnancy, MTHFR gene mutations have been studied in relation to fertility and pregnancy outcomes. Research suggests that women with certain MTHFR variants, especially C677T homozygous, may have higher homocysteine levels and potentially an increased risk for complications, such as:

• Neural tube defects (NTDs): Low folate activity during early pregnancy is linked to a higher risk of NTDs in the baby.
• Recurrent pregnancy loss or miscarriage: Some studies suggest a possible association between MTHFR variants and miscarriage risk, although findings are mixed.
• Preeclampsia and other complications: Elevated homocysteine has also been associated with preeclampsia and other adverse outcomes.

That said, most health organizations do not recommend routine MTHFR testing in pregnancy, since evidence is not strong enough to change standard care. What’s universally recommended, however, is that women of childbearing age get enough folate.

Many practitioners encourage supplementation with methylated folate (5-MTHF) instead of folic acid, since it bypasses the MTHFR enzyme step and is more bioavailable for those with mutations.

Natural treatments

1. Consume more natural folate, vitamin B6 and vitamin B12

Acquiring more folate and other methylated vitamins can help with methylation. Getting more folate is very different than taking some folic acid supplements, however.

Some research even suggests that people with MTHFR mutations might have a harder time converting synthetic B9 (folic acid) into its usable form and actually experience worsened symptoms from taking supplements containing folic acid.

Getting enough folate is especially important before and during pregnancy. In the three months before conception and during the first trimester of pregnancy, mothers who get enough folate lower their children’s risk for various health problems.

Look for the bioavailable forms of folate in supplements called l-methylfolate or fermented folic acid, which are both processed by the body more like folate, and consume plenty of foods with folate.

L-methylfolate is harder to pack into capsule form, so you may not be able to get very high doses in typical multivitamins or supplement blends. That’s taking supplements with fermented folic acid, which is biotransformed into whole-food form by friendly yeast, is a good idea.

Having more folate in your diet means you’re better able to create the active form of 5-MTHF. Some of the best high-folate foods include:

• Beans and lentils
• Leafy green vegetables like raw spinach
• Asparagus
• Romaine
• Broccoli
• Avocado
• Bright-colored fruits, such as oranges and mangoes

Those with a MTHFR mutation are also more likely to be low in related vitamins, including vitamin B6 and vitamin B12. These are easier to obtain from supplements, but food sources are always best.

To get more B vitamins, focus on eating enough quality protein foods, organ meats, nuts, beans, nutritional yeast and raw/fermented dairy products.

2. Treat digestive problems

Digestive complaints are common among people with MTHFR A1298C mutations. Many things affect digestive health, including nutrient intake, inflammation levels, allergies, neurotransmitter levels and hormone levels.

For people who are already prone to nutrient deficiencies, leaky gut syndrome can make problems worse by interfering with normal absorption and raising inflammation.

To improve digestive/gut health, the following dietary adjustments can be very beneficial:

• Reduce intake of inflammatory foods, such as gluten, added sugar, preservatives, synthetic chemicals, processed meats, conventional dairy, refined vegetable oils, trans fats and processed/enriched grains (which often include synthetic folic acid).
• Increase intake of probiotic foods, which are fermented and supply “good bacteria” that aids in digestion.
• Consume other gut-friendly foods, including bone broth, organic vegetables and fruit, flaxseeds and chia seeds, and fresh vegetable juices.
• Focus on consuming healthy fats only, like coconut oil or milk, olive oil, grass-fed meat, wild-caught fish, nuts, seeds, and avocado.

3. Manage anxiety and depression

Because of how it can negatively affect levels of neurotransmitters and hormones like serotonin, testosterone and estrogen, MTHFR mutations are tied to higher incidences of mental disorders, including anxiety, depression, bipolar disorder, schizophrenia and chronic fatigue. High levels of stress can also make MTHFR mutation symptoms even worse.

Tips for dealing with these conditions include:

• Supplementing with omega-3 fatty acids: Omega-3s help reduce inflammation and are beneficial for cognitive health.
• Regularly practicing natural stress relievers: These include meditation, journaling, spending time outside, giving back or volunteering, praying, etc.
• Regularly exercising: Helps improve hormonal balance and sleep quality.
• Using soothing essential oils, including lavender, chamomile, geranium, clary sage and rose.
• Eliminating use of recreational drugs and reducing alcohol intake, which can both make symptoms worse by interfering with methylation.

4. Protect heart health

Studies show that homocysteine levels tend to rise with age, smoking and use of certain drugs, so the first step is to focus on taking care of yourself as you get older and limiting use of harmful substances.

Other tips for keeping your heart healthy include:

• Eating a healthy diet, especially one with plenty of high-fiber foods
• Getting regular exercise and keeping your weight in a healthy range
• Managing stress to prevent worsened inflammation
• Consider taking the following supplements, which can help improve blood flow, cholesterol and blood pressure: magnesium, omega-3s, CoQ10, carotenoids and other antioxidants, selenium, and vitamins C, D and E.

5. Discuss your medications with a doctor

Some medications can further deplete already low folate levels or interfere with methylation. Speak with your doctor if you take any of the following drugs, which might make symptoms worse:

• Antibiotics, specifically sulfa-containing drugs like sulfamethoxazole and trimethoprim (SEPTRA or Bactrim), sulfasalazine or triamterene (found in Dyazide)
• Birth control pills
• Hormone replacement therapy drugs
• Anticonvulsants (like phenytoin and carbamazepine)
• Antacids/acid blockers
• NSAID pain relievers
• Antidepressants
• Chemotherapy treatments
• Cholesterol-lowering drugs (like niacin, acid sequestrants, cholestyramine, colestipol and colesevelam)
• Nitrous oxide (typically during dental work)
• Methotrexate for rheumatoid arthritis
• Metformin for diabetes and PCOS

6. Boost detoxification

Because reduced methylation contributes to poor elimination of heavy metals and toxins, take extra steps to help flush waste and accumulated chemicals from your body. Tips for improving your ability to detox include:

• Consuming fresh vegetable juices to increase antioxidant intake
• Taking activated charcoal
• Drinking plenty of water and avoiding alcohol or tobacco
• Dry brushing
• Taking detox baths
• Exercising regularly
• Sitting in saunas
• Occasionally fasting in a healthy way or using natural enemas
• Only using natural beauty and household products that are free from harsh chemicals

7. Get enough quality sleep

Sleep disturbances are common among people with anxiety, hormonal disorders, autoimmune disorders, chronic pain and fatigue. Make it a priority to get seven to nine hours every night, sticking to a regular schedule as much as possible.

To help you get better sleep, try natural sleep aids like:

• Create a relaxing bedtime routine
• Use essential oils
• Stay off of electronic devices
• Read something soothing
• Cool your bedroom a bit, and make it very hard

Precautions

As mentioned above, MTHFR mutations are genetic and inherited. Developing problems from a mutation is not guaranteed.

If you have a personal or significant family history of one or more of the above illnesses, it’s probably worth speaking with your medical provider about being tested for a MTHFR mutation.

To be clear, MTHFR genetic mutations are not the only type that are capable of changing the way that methylation is carried out or homocysteine is converted. This is part of what makes researching disorders related to this mutation difficult.

Before assuming that MTHFR mutations are the cause of any of your symptoms, get confirmation through testing and discuss results with your doctor. Don’t change medications without guidance, and get a second opinion if advice you receive seems unsafe.

Frequently asked questions

What does MTHFR stand for?

MTHFR stands for methylenetetrahydrofolate reductase. This is an enzyme that plays a critical role in how your body processes folate and homocysteine, two key factors in methylation, DNA synthesis and overall metabolic health.

What does it mean to have a MTHFR gene mutation?

It means you carry a genetic change that may reduce the efficiency of the MTHFR enzyme, which helps process folate and regulate homocysteine.

How common is an MTHFR mutation?

Very common. Up to 40 percent to 50 percent of people may carry at least one variant (or even more), though most will not experience significant health issues.

What are symptoms of MTHFR gene mutation?

Most people with a mutation have no obvious symptoms. However, in some cases, possible symptoms linked to poor methylation or high homocysteine may include fatigue, brain fog, headaches, mood changes, fertility struggles or cardiovascular concerns. These are nonspecific symptoms, so testing and medical evaluation are important.

Should I get tested for an MTHFR gene mutation?

In most cases, testing is not necessary. Doctors are more likely to measure homocysteine levels, which reflect how well methylation is functioning in your body.

If I have a mutation, what supplements should I take?

Methylated folate (5-MTHF), vitamin B12 and other B vitamins may help support methylation. Work with your healthcare provider to determine what’s best for you.

What foods should you avoid if you have MTHFR mutation?

It’s best to minimize foods fortified with synthetic folic acid, since your body may not process it efficiently. Instead, focus on natural folate-rich foods like leafy greens, legumes, asparagus, avocados and liver. Highly processed foods, excess alcohol and foods high in refined sugar may also hinder methylation.

Can MTHFR cause B12 deficiency?

An MTHFR mutation itself doesn’t directly cause vitamin B12 deficiency, but it may increase the body’s demand for B12 in its active form (methylcobalamin) to keep methylation pathways running efficiently. Supporting both folate and B12 is important if you carry a variant.

Does having a mutation mean I’ll develop health problems?

Not necessarily. Many people with MTHFR mutations live healthy lives. Diet, lifestyle and other factors play a big role in whether the mutation has any effect.

Final thoughts

• MTHFR mutations are caused from inheriting one or more mutated genes that interfere with the normal process of methylation, folate conversion and enzyme production.
• Health conditions associated with MTHFR mutations include autism, ADHD, fertility problems, depression, heart problems, mood disorders and autoimmune disorders.
• Other factors can also make MTHFR mutation symptoms worse by further decreasing folate levels and raising homocysteine levels, including eating a poor diet, leaky gut syndrome/poor absorption, malnutrition, gastrointestinal illness, high amounts of stress, alcohol and drug use, and toxin exposure.
• Natural treatments and ways to manage MTHFR symptoms include improving gut health, getting more natural folate from your diet, acquiring more vitamin B6 and B12, exercising, lowering intake of inflammatory foods, and managing stress.