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New to MTHFR Gene Mutation Symptoms? Here's How Stress Can Affect Your Methylation

New to MTHFR Gene Mutation Symptoms?

New to MTHFR Gene Mutation Symptoms? Here's How Stress Can Affect Your Methylation


If you’re just learning about MTHFR and how it can affect your health, you may be somewhat overwhelmed. MTHFR is a complicated topic and there’s a ton of information out there. But this blog will help clear things up. 

First, you need to understand methylation. Methylation is a process that occurs in every cell in your body and drives nearly every bodily system. MTHFR is a gene that “switches on” the methylation process. However, a mutation on the MTHFR gene can have major implications for your mental health and physical function. 

Let’s look at how stress can affect your body’s methylation process and what you can do to support your health.

Understanding the MTHFR gene mutation

The MTHFR gene can mutate at several different positions, but the most common is at position 677. This results in an amino acid change from alanine to valine in the enzyme, and is known as C677T. The C677T mutation affects homocysteine levels and can increase the risk of elevated homocysteine (hyperhomocysteinemia), low folate levels, and several cardiovascular diseases.  [1] MTHFR enzyme activity is usually around 50–60% lower in people with C677T. 

Another common MTHFR variant is A1298C, due to the mutation occurring at position 1298 on the MTHFR gene. This mutation also results in reduced enzyme activity although not to the same extent as C677T.

The impact of MTHFR gene mutation on the methylation process

The MTHFR gene provides instructions to your body for making methylenetetrahydrofolate reductase, an enzyme that plays a crucial role in converting folic acid (vitamin B9) into folate. Folate is required for a multistep process that converts homocysteine to methionine, which is then required to make many other proteins, neurotransmitters, and other important compounds. [2]

A mutation on the MTHFR gene reduces the activity of the enzyme, which impairs the methylation process. This then affects numerous downstream processes required by the body to function properly. 

Symptoms and health risks associated with MTHFR gene mutation

Depending on the type of MTHFR mutation, those affected may be at risk of certain symptoms and health issues. Clinical symptoms associated with MTHFR-deficient patients may include developmental delay as well as various neurological and vascular issues, such as: [3]

Depression and other mood disorders

• Thrombosis and vascular lesions

• Hyperhomocysteinemia: Both C677T and A1298C have been implicated in causing elevated homocysteine levels, which is a risk factor for cardiovascular diseases and stroke. [4]

• Homocystinuria: a disorder caused by the inability to metabolize homocysteine and create methionine

• Migraine

• Recurrent pregnancy loss

• Neural tube defects and congenital anomalies

• Some cancers

• Neurodevelopmental disorders

• Insomnia

• Chronic fatigue

The connection between stress and methylation

Stressors are known to alter the expression of genes and cellular processes that influence behavior. 

Stress (i.e. job strain, loss of a loved one, illness diagnosis) is a risk factor for cardiovascular disease, with increased risk of coronary heart disease mortality in those who experienced three or more stressful life events. Exposure to stress can alter the normal pattern of DNA methylation, which may then alter certain genes and increase the risk of various diseases.  [5] Stress during early life, such as childhood abuse and stress-related disorders, have lasting effects on methylation that may persist into adulthood.

Chronic stress can lead to the accumulation of epigenetic changes such as DNA methylation. In other words, stress can cause changes to genes that are involved in how we think and act. 

The brain is more sensitive to plasticity at certain points throughout development. According to some researchers, this can mean that if someone is affected by severe stress during a particular developmental period, they may be more vulnerable to epigenetic alterations that can increase their risk of certain diseases. [6]

Studies in mice have shown that DNA methylation patterns can be altered by chronic stress, leading to long-term changes in certain genes. Mice exposed to stress have decreased methylation, resulting in genetic changes that cause anxiety and depressive-like behavior.  [7]

Some studies have shown that people living in a disadvantaged neighborhood as children tend to experience increased DNA methylation of the genes involved in stress and inflammation later in life.  [8] The cumulative exposure of this stress is reported to affect methylation. 

A systematic analysis found that animals that were physically, psychologically, and socially stressed had reduced methylation. These results are consistent with previous research showing that stressors such as childhood abuse and social environment can modify the methylation process that regulates normal brain function. [9]

Symptoms and health risks associated with chronic stress and impaired methylation

Early-life stress, such as childhood abuse and stress-related disorders, have lasting effects on methylation that may persist into adulthood. 

Some research has shown that stress or trauma experienced in childhood may be associated with health issues such as heart disease and type 2 diabetes in adults. [10]

Stress is also shown to lead to changes in genes that have both immediate and future effects on brain function. Some research has suggested that chronic changes to genes in certain brain regions may lead to cognitive changes that result in behaviors such as anxiety and addiction. [11]

Coping strategies for stress and supporting methylation

While it may not be possible to avoid stress completely, we can minimize its effects on the body and mind. 

• Practice mindfulness

Mindfulness can influence stress pathways by changing brain structures and activity in regions associated with attention and emotion regulation. A large meta-analysis found that mindfulness helped significantly reduce anxiety, depression, psychological distress and stress levels. [12]

Simple mindfulness techniques can be sourced online or with apps, or in activities such as yoga and meditation.

• Be physically active

Engaging in physical activity on a regular basis is shown to result in better mood, less stress, and less negative affect. By contrast, low levels of physical activity are related to higher stress and negative affect, as well as lower positive affect.

Physical exercise can be anything that increases the heart rate for at least 30 minutes. Walking, jogging, swimming, dancing, or even household chores are all forms of exercise.


Dietary recommendations for supporting healthy methylation

Active B vitamins (specifically vitamin B9 (folate), B6, and B12)

B vitamins play a crucial role in the methylation process, and active Bs are the only form that can bypass the MTHFR mutation. 

Folate and other B vitamins can be sourced from a range of foods, including:

• Leafy greens

• Broccoli

• Legumes and beans

• Clams

• Avocado

• Red meats

• Whole grains

• Nuts and seeds

• Dairy products


Antiinflammatory foods

An anti-inflammatory diet can help to reduce homocysteine and systemic inflammation. This means plenty of fresh fruits and vegetables, olives, healthy fats (fatty fish, avocado, olive oil), and low intake of sugar. Antioxidant-rich foods can help reduce free radical damage (which is linked to inflammation), and improve detoxification while supporting overall gut health.

• Oily fish

• Brightly-colored fruits

• Leafy greens

• Nuts

• Seeds

• Other whole foods (organic where possible)

Supplement recommendations for MTHFR support

While a balanced diet should form the basis of any healthy lifestyle, nutritional supplements can be a more effective source of concentrated nutrients. Those with MTHFR need to supplement with methylfolate and active vitamin B12, as these two nutrients have been clinically proven to assist with the methylation cycle more effectively than their inactive forms. Research shows that methylfolate bypasses the MTHFR mutation and is more bioavailable than folic acid. [13]  The nature-bioidentical forms of B12 (methylcobalamin, hydroxocobalamin, and adenosylcobalamin) are superior in bioavailability and safety to cyanocobalamin. [14]

Methylfolate and active B12 are available in Methyl-Life’s Mood Elevating bundle. This includes a therapeutic dose of L-Methylfolate (15 mg) plus B12 Complete, which contains all three forms of active B12. Taken together, methylfolate and B12 can promote healthy mood and support the body’s stress response, helping to minimize the effects of chronic stress and anxiety. 

Seeking professional support

If you’re suffering from symptoms that affect your quality of life, or you’re struggling to do the things you normally would, it’s imperative that you seek help from a qualified health practitioner. Your doctor or other licensed practitioner can assess your symptoms and provide the medical advice you need. 

If you suspect you have a MTHFR gene mutation, you may request genetic testing to determine this. A diagnosis can then help steer you in the right direction for nutritional support and other health advice. 

The takeaway

Understanding MTHFR and how it may affect your health is the first step in managing symptoms. If diagnosed with a C677T or A1298C polymorphism, you can be proactive in supporting your long-term health through diet, supplementation, and healthy lifestyle habits. Methylfolate and active B12 are an essential part of your body’s methylation process, and are best obtained from quality supplements. Managing stress is also crucial for optimizing wellbeing and reducing your risk of ill health later in life. 

















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    Written By,
    - Katie Stone



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