MTHFR Gene Mutation: Symptoms and Physical Signs

MTHFR Gene Mutation: Symptoms, Physical Signs, and What to Know

Introduction to MTHFR Gene Mutation

Methylenetetrahydrofolate reductase (MTHFR) is an enzyme in the human body that helps break down folate (vitamin B9). It also helps the body regulate homocysteine, which is an amino acid involved in mental health as well as proper heart functioning. 

Not everyone has the same genetic code, and that includes the MTHFR gene. Some people inherit a form of the gene that may place them at higher risks for developing certain diseases, as discussed below. 

What is the MTHFR Genes

The MTHFR enzyme plays a key role in methylation. Methylation is an important chemical reaction in the body that is important for fixing damaged DNA, expression of genes, synthesis of neurotransmitters such as dopamine, serotonin, and norepinephrine, and heart function. Proper functioning of these processes ensure that our bodies are at optimal physical and mental health. 

How MTHFR Mutations Affect the Body

We all inherit two copies of each gene from our parents, one from mom and one from dad. If one copy has a mutation, this is known as heterozygous. If both copies are affected by a mutation, this is known as homozygous. If there is no mutation in either copy, the gene functions normally. Genes code for different proteins in the body, which include enzymes. MTHFR is an important enzyme that requires two healthy copies in order to function at optimal levels. If you are heterozygous for a certain mutation, the MTHFR enzyme functions at mildly reduced capacity. If you are homozygous, the MTHFR enzyme functions at a significantly reduced capacity. 

Reduced activity of the MTHFR enzyme can lead to elevated levels of the amino acid homocysteine and lower levels of folate. Read below for more detail on how this affects brain and body functioning. 

How MTHFR Mutations Affect the Body

There are two main mutations that can affect the body: 

C677T 

A1298C 

The C677T mutation has been associated with increased risk for the development of certain psychiatric disorders, such as schizophrenia, severe depression, and bipolar disorder. 

The A1298C mutation by itself has not been shown to have significant effects on disease risk, but when combined with the C677T mutation, MTHFR enzyme activity is significantly reduced. 

It is important to note that mutations in the MTHFR gene do not cause mental illness, rather they predispose an individual to developing certain conditions. For a person to develop a disease, the mutation, which increases their susceptibility, is usually combined with environmental (stress, trauma, etc) and other genetic factors. 

 Symptoms of MTHFR Gene Mutation

There are many signs and symptoms that may indicate an MTHFR mutation. It is important to state, however, that some people with MTHFR mutations have no symptoms at all. In addition, having the below symptoms does not mean you necessarily have an MTHFR mutation. 

Some signs and symptoms include: 

-Cognitive instability (brain fog)
-Affective instability (moodiness)
-Migraine with aura (headache with prior visual or sensory disturbances)
-Anxiety, panic attacks
-Fatigue or insomnia (excessive sleepiness or difficulty falling or staying asleep)

These symptoms may be due to impairments in synthesis of neurotransmitters as mentioned above. Neurotransmitters are chemicals in the brain that play a role in brain cell (neurons) communication to regulate mood and cognition. The MTHFR enzyme is involved in the synthesis of dopamine, serotonin, and norepinephrine, all of which pay a role in mental health. 

 Physical Signs to Watch For

People with MTHFR mutation may have subtle or nonspecific symptoms, that may also be influenced by other factors. Some of these symptoms include chronic fatigue, headaches, or pale skin tone. This is because the MTHFR enzyme helps the body form red blood cells and plays a role in detoxification. Thus, if the MTHFR enzyme is not functioning optimally, some of these symptoms may appear. 

Common Health Issues Linked to MTHFR Mutations

Common health conditions associated with MTHFR mutations include depression, anxiety, cardiovascular disease, and migraines. 

Numerous studies have shown that the MTHFR C677T mutation, particularly homozygosity, where a patient inherits both mutated copies of the gene, form, is linked to a modest but measurable increase in cardiovascular disease (CVD) risk, primarily through its impact on homocysteine metabolism. Elevated levels of homocysteine can cause downstream effects of injuring blood vessels and leading to increased inflammation, which can ultimately lead to CVD. When combined with the C677T mutation, the A1298C variant may have an additive risk, but does not have an increased risk individually. 

 Causes and Risk Factors

MTHFR mutations are inherited, meaning they are passed down through DNA from generation to generation. Whether or not they cause health problems depends on lifestyle. The mutation alone may not cause health issues as described above, but symptoms may occur when the mutation is combined with inadequate folate intake, high stress, or environmental exposures. 

 Genetic Factors

Every gene in the human body has two copies, one inherited from the mother and one from the father. If one copy is mutated, this is known as heterozygous. If both copies are mutated (with either the same or a different mutation), this is known as homozygous (if the same mutation), or compound heterozygous (if different mutation). 

 Environmental and Lifestyle Factors

Certain external factors can amplify the effects of an MTHFR mutation. Low intake of natural folate (such as from leafy greens), chronic stress, excessive alcohol use, smoking, and exposure to environmental toxins can all impair MTHFR enzyme function and increase homocysteine levels in the body. Poor sleep, excess inflammation, or a diet rich in processed foods can also worsen symptoms related to the MTHFR mutation. 

Diagnosis and Testing

Testing for MTHFR mutations is simple and non-invasive, and usually only requires a sample or saliva.  The goal of genetic testing is to understand your individuality and how your body processes nutrients, such as folate. You can then take this information to optimize your lifestyle and add supplements to help with symptoms accordingly.

How MTHFR Testing Works

There are many different genetic tests. EvoDNA provides one such test, where a saliva sample can provide information about your MTHFR gene and whether or not you carry mutations that can increase your risk for certain symptoms or conditions

Understanding Your Test Results

If you test positive for one or both MTHFR variants, it doesn’t automatically mean you will develop or already have the health conditions described above. It means that you are “predisposed” or more susceptible because your MTHFR enzyme may not be functioning as efficiently. A heterozygous result indicates that you have one copy of the mutated gene, whereas a homozygous result indicates that you have two copies of the mutation gene. A homozygous or compound heterozygous (one copy of two different mutations) indicate that you may have a higher risk of elevated homocysteine levels or disrupted folate metabolism. Results should be interpreted with your medical history by a qualified provider.

Treatment and Management

If you have a MTHFR gene mutation, you cannot change that. The genes we inherit from our parents are permanent. You can, however, alter your lifestyle to reduce health outcomes associated with this mutation. With the right nutrition, supplementation, and lifestyle habits, many people with MTHFR variants experience improved energy, mood, and overall health. Supplementation with vitamin B2, vitamin B6, and vitamin B12, as well as a diet rich in leafy greens, can help. In addition, reducing alcohol consumption and smoking cessation may lower homocysteine levels in the body. 

 Lifestyle Changes and Diet

The MTHFR mutation may cause reduced folate levels in the brain and body. To naturally increase this, you can eat more foods that contain folate, such as leafy greens, beets, lentils, and avocado. Regular exercise, adequate hydration, sufficient sleep, and managing stress can optimize your body’s methylation and lower homocysteine levels.

Supplements and Medical Approaches

Supplementation with L-methylfolate (the active form of folate) and methylcobalamin (vitamin B12) can help bypass the inefficiencies in the enzyme pathway caused by the MTHFR mutation. Some individuals also benefit from adding riboflavin (vitamin B2), vitamin B6 to further support neurotransmitter synthesis and detoxification pathways in the body. Always consult a clinician familiar with genetic and nutritional medicine before starting any new supplement.

MTHFR and the developing baby

You may have heard that pregnant women must ensure the proper amount of folate to ensure proper development of the fetus. Adequate folate intake is essential during early pregnancy to support DNA synthesis and cell division in the developing neural tube, which ultimately forms the baby’s brain and spinal cord. Mutations in the MTHFR gene, such as C677T and A1298C (although to a lesser extent), can lower the MTHFR enzyme’s ability to covert folate from the diet into the active form that helps the body function properly. The active form of folate is L-methylfolate, and can be taken as a supplement (prenatal vitamins). 

Studies have shown that women with MTHFR mutations that reduce the function of the MTHFR enzyme, as well as low folate intake, have increased risk of neural tube defects in the baby. Neural tube defects can be detrimental to a developing fetus. This risk is preventable by folate supplementation, especially formulations with the active form of folate (L-methylfolate), even in women with MTHFR mutations.  

 Frequently Asked Questions (FAQ)

How to know if you have MTHFR gene mutation?

The only way to confirm is by genetic testing. 

How many people have MTHFR gene mutation?

In the U.S., roughly 1 in 4 people have a moderate reduction in enzyme function due to MTHFR mutation. Testing is particularly worthwhile for individuals with family histories of cardiovascular disease or depression. MTHFR mutations are quite common throughout the world, with up to 40% of the global population carrying at least one mutated copy. 

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