What is a MTHFR gene mutation?

MTHFR stands for Methylenetetrahydrofolate Reductase, which refers both to an enzyme and the gene responsible for its production. The MTHFR enzyme plays a crucial role in the methylation process, where it converts folate (vitamin B9) from the foods we eat into its active form, methylfolate (L-5-MTHF).

Methylfolate is essential for several biological processes that influence mental, cardiovascular, and overall health.

The body relies on this enzyme to facilitate critical functions, including:

• DNA synthesis and repair: Ensuring cells grow and replicate correctly.
• Detoxification: Helping the body eliminate harmful substances.
• Homocysteine regulation: Keeping homocysteine levels balanced, which is crucial for heart health.
• Neurotransmitter production: Supporting the synthesis of mood-regulating chemicals like serotonin and dopamine.
• Producing SAMe from methionine: SAMe is required for the production of neurotransmitters. 
• Supporting glutathione production: Glutathione is the body’s major detoxifier. 
• Fertility health: Support for preconception and pregnancy
• Fetal development: Ensures the proper development of the baby’s brain and spinal cord
• Cognitive function: Supports the myelin sheath, blood-brain-barrier function and neurotransmitter production

The MTHFR gene, which instructs the body to produce the MTHFR enzyme, can sometimes undergo mutations. These mutations can alter the enzyme’s effectiveness, potentially leading to health issues, earlier for some and over time for others.

MTHFR mutations come in two primary forms:

• Heterozygous: A person inherits one copy of a mutated MTHFR gene from each parent. This means they carry one variant of either of the common SNPs (single nucleotide polymorphisms) C677T or A1298C.

• Homozygous: A person inherits two copies of the same mutation SNP, either two C677T or two A1298C variants. Homozygous mutations may result in more significant disruptions in methylation.

People with compound heterozygous mutations, which means they carry one C677T and one A1298C mutation, can also experience issues with methylation. An MTHFR test will reveal the exact variant of MTHFR.

When the MTHFR enzyme doesn’t work properly, your body can’t process folate efficiently, leading to:

• Elevated homocysteine: High levels of homocysteine can increase the risk of cardiovascular diseases such as heart attacks, strokes, and blood clots.

• Reduced methylation: Methylation is vital for detoxification, neurotransmitter production, and overall cell health. A compromised methylation process can result in imbalances in neurotransmitters, contributing to mental health issues like anxiety and depression. Poor methylation can also lead to high homocysteine and several cardiovascular diseases. In pregnancy, a lack of folate can lead to pregnancy loss and neural tube defects, and has also been linked to a higher risk of behavioural disorders such as autism and ADHD.³

It’s important to note that having an MTHFR mutation doesn’t guarantee you’ll experience health problems. Environmental factors, diet, and lifestyle can all play key roles in determining how problematic genetics become as well as how to treat the MTHFR gene mutation.

MTHFR mutations are inherited from both parents, meaning you can receive a defective gene from either your mother or father. This inheritance pattern explains why some individuals are heterozygous while others are homozygous for MTHFR mutations.

The controversy surrounding MTHFR stems from conflicting medical opinions. While many healthcare providers acknowledge the potential health impacts of MTHFR mutations, others remain skeptical, especially given the wide range of individual responses to the mutation. Some doctors believe that MTHFR’s influence on health is overstated and that many individuals with mutations live healthy, symptom-free lives. Nevertheless, MTHFR mutations can be a significant concern for those who experience adverse health effects, particularly related to cardiovascular and neurological issues.

There is no direct evidence to suggest that MTHFR mutations significantly reduce life expectancy unless in the case of triple and quadruple mutation combinations. These are unlikely to survive in the embryo.⁴

However, the health conditions associated with elevated homocysteine—such as heart disease and stroke—can be life-threatening if left unmanaged. Therefore, addressing homocysteine levels and supporting methylation can help mitigate long-term health risks.

It should also be noted that MTHFR is linked to severe depression, which in turn is linked to many chronic and deadly diseases, self-harm, and suicide. 

It is estimated that 30-60% of the global population has an MTHFR mutation, making it one of the most common genetic mutations. Despite this high prevalence, not everyone with an MTHFR mutation will experience symptoms or health issues. It’s the combination of genetic predisposition, environmental factors, and lifestyle choices that determines how significantly an MTHFR mutation affects an individual.

The MTHFR gene C677T mutation affects around 25% of the global population, with those of Hispanic descent representing the highest frequency (47%), followed by Europeans at 36%. The MTHFR 1298AC mutation is also present in about 25% of the global population, occurring most frequently in those of South East Asian descent (42%) and Europeans (31%).⁶