The Ultimate Guide to the MTHFR Gene Mutation: Symptoms, Treatment, and Testing
The MTHFR gene mutation is an increasingly popular topic and with good reason. The C677T mutation affects an estimated 30-40% of the US population, while another 14% may have the A1298C mutation. Both mutations are associated with a wide range of health concerns and can have major implications for an individual's wellbeing if untreated.
Unfortunately, the internet is rife with unsubstantiated claims about MTHFR, making it difficult to identify or manage your health concerns.
This guide will cover everything you need to know about the MTHFR gene mutation and what it really means. We’ll also explain the symptoms associated with MTHFR and provide verified resources to help you learn more about it.
What is the MTHFR Gene?
The MTHFR gene instructs your body to produce the MTHFR enzyme. MTHFR stands for methylenetetrahydrofolate reductase, an enzyme required for processing folate (vitamin B9) into its active form so the body can use it.
MTHFR also plays a major role in:
Methylation is the transfer of methyl groups between different bioactive compounds in the body.
To function properly, these compounds—such as proteins, enzymes, and hormones—must be methylated.
Methylation is also required for your body to produce vital nutrients such as folate, vitamin B12, amino acids, neurotransmitters, hormones, red blood cells, DNA, RNA, and certain antioxidants.
These nutrients play crucial roles in how your body functions, particularly your heart, brain, reproductive system, detoxification pathways, and so on.
A normal, healthy MTHFR gene contains the DNA code for synthesizing the MTHFR enzyme.
However, errors can occur in this gene code, causing part of the DNA sequence to vary. This is called "single nucleotide polymorphism" (SNP), a variant, or a mutation. As a result, the MTHFR enzyme doesn’t function as well as it should.
To learn more, check out these in-depth guides:
MTHFR Gene Variants
The degree of MTHFR deficiency depends on the type of SNP and how many are present in the MTHFR genes.
Each MTHFR gene comprises a pair of alleles, one inherited from each parent. Because there are two locations on the MTHFR gene where variants can occur, a mutation could be on just one gene (heterozygous)or both (homozygous).
An example of two MTHFR variants include:
C677T: This is a mutation at position 677 onthe MTHFR gene. It affects an estimated 25% of the global population, with ahigher prevalence in those of Hispanic descent.
A1298C: This mutation occurs at position 1298on the MTHFR gene. It’s less common, and less is known about its implications.
C677T and A1298C can affect a carrier’s health differently, and you can learn more about this here.
MTHFR Gene Mutation Symptoms and Complications
Clinical symptoms of MTHFR include developmental delay and various neurological and vascular problems, such as seizures, thromboses, and vascular lesions.
Other symptoms associated with MTHFR gene mutations include:
Behavioral disorders:ADHD, autism
Long-term health complications associated with MTHFR are known to include:
Cardiovasculardisorders: Stroke, heart attack, deep vein thrombosis
Cardiovascular issues:high blood pressure, thromboembolic disorders
How MTHFR May Impact Other Health Conditions
MTHFR deficiency and impaired methylation may also impact existing health conditions.
Mood disorders such as depression and anxiety are among the most common conditions associated with MTHFR mutations. Low or deficient methylfolate impairs the body’s ability to produce the neurotransmitters required for a healthy mood, increasing the risk of developing anxiety and depression.
Poor neurotransmitter production has also been associated with a higher prevalence of insomnia, adrenal fatigue and fibromyalgia in adults, and behavioral disorders in children, particularly ADHD and autism.
The gut microbiome is closely connected with the central nervous system (CNS), and the toxic accumulation of homocysteine has been implicated in Candida infections.
Vitamin B12 and folate are crucial for red blood cell production, and low levels can increase the risk of anemia. These nutritional deficiencies also result in elevated homocysteine levels, which can then lead to cardiovascular disorders such as stroke, gout, and blood clots.
Elevated homocysteine also appears to play a major role in the development of serious illnesses such as multiple sclerosis and lupus.
MTHFR is also associated with thyroid disorders such as Hashimoto’s disease(hypoactive thyroid) and Graves’ disease (hyperactive thyroid) due to a genetic susceptibility that involves shared genes and pathways affecting thyroid T cells.
Poor homocysteine regulation also appears to be prevalent in estrogen-related disorders such as polycystic ovarian syndrome (PCOS), although it may not be a direct cause. Infertility and weight gain have also been linked to estrogen and MTHFR.
Testing for MTHFR
Finding out whether you are affected by an MTHFR mutation may help to explain certain symptoms or health issues, such as high homocysteine or depression. This makes it possible to explore options for supplementation and other treatment.
Testing methods for identifying an MTHFR mutation include saliva tests, genetic blood test, and/or a DNA panel test.
Each method varies significantly in terms of cost and the amount of information that can be obtained about your genetics.
More information about the pros and cons of these tests can be found in these guides:
An MTHFR mutation won’t necessarily result in the symptoms or health issues described above. Most patients with MTHFR seek treatment to correct nutritional deficiencies and/or to assist with issues such as depression, high homocysteine, or infertility.
Treating these issues requires a multi-pronged approach encompassing diet, supplementation, and lifestyle changes. In some cases, medication may be necessary.
Folate (vitamin B9) is essential for healthy methylation. It is typically low in those with MTHFR mutations due to the body’s inability to activate folic acid. Supplementing with methylfolate is highly recommended as it is an active form of folate that can bypass the MTHFR genetic mutation and participate in methylation reactions.
Methylcobalamin (active vitamin B12)
B12 works alongside the enzymes that use folate to generate and utilize methyl groups, including the conversion of homocysteine to methionine.
Pyridoxal 5’-Phosphate (active vitamin B6)
Pyridoxal 5'-phosphate (P5P) is also required for the break-down of homocysteine to taurine and cysteine, hemoglobin production, and the healthy formation of the myelin sheath that surrounds and protects nerve cells.
Increase dietary intake of folate
Folate (in its natural form) is naturally present in several foods. Good sources include vegetables (especially dark leafy greens), brightly-colored fruits, nuts, seeds, beans, eggs, dairy products, beef, poultry, seafood, and grains.
Increase dietary intake of vitamin B12
Food sources of B12 include animal products such as fish, beef, poultry, eggs, milk, and other dairy products.
What to Avoid
Those with MTHFR gene mutations must avoid folic acid. It is a synthetic form of folate used in many commercial supplements, pharmaceutical prescriptions, and fortified foods and is absorbed less well than folate and methylfolate. Those with MTHFR gene mutations lack the enzyme required to activate folic acid, which can result in the accumulation of unmetabolized folic acid.
Dealing with High Homocysteine
Homocysteine is a chemical in the blood formed when the amino acid methionine is metabolized. Vitamins B12, B6, and folate are required to recycle homocysteine back into methionine so it can be used to build other proteins.
However, deficiency in the MTHFR enzyme means that the body will also be low or deficient in 5-methyltetrahydrofolate(the active form of folate required for metabolizing homocysteine) as well asB12 and B6. As a result, homocysteine cannot be efficiently recycled and builds up the blood.
Elevated homocysteine can severely damage the lining of the arteries, increasing the risk of cardiovascular issues such as atherosclerosis (hardening of the arteries) and the development of blood clots in the arteries and veins.
High homocysteine has also been linked to other vascular disorders, including cognitive decline and dementia, mood disorders(depression, anxiety), chromosomal defects, osteoporosis, migraines, polycystic ovarian syndrome, and multiple sclerosis.
Reducing homocysteine levels is crucial, especially for those with MTHFR. This is best done through a combination of dietary changes and supplementation.
Treating MTHFR During Pregnancy
Folate is crucial for the healthy development of the fetus. Women with an MTHFR gene mutation who have low folate levels are at a higher risk for pregnancy complications such as preeclampsia and miscarriage. They also risk having a baby with neural tube defects, chromosomal abnormalities, or other developmental issues.
Women planning to start a family should know which form of folate to take before and during pregnancy, especially if they have an MTHFR mutation. They must also take the right prenatal vitamins to support their own and their baby’s health. It is also crucial that they first discuss any supplementation or dietary changes with their doctor.
Diet Considerations for MTHFR Mutations
Diet plays a major role in supporting good health, and the right foods can help to maintain important nutrient levels.
Those with MTHFR are encouraged to follow an MTHFR treatment diet that may help reduce the risk of MTHFR-related diseases and conditions. Eating the right foods is particularly important for vegans and those with allergies or gluten sensitivities.
Although food cannot provide the same folate levels as a supplement, folate-rich foods can help support the methylation cycle. There are also plenty of foods that provide valuable vitamins and minerals that assist in managing homocysteine levels and overall good health.
Supplementation for MTHFR
As mentioned previously, those with MTHFR gene mutations are at a higher risk of deficiencies in folate and vitamin B12: two of the most crucial nutrients involved in proper methylation.
The most effective way to restore and maintain healthy levels of these vitamins is through supplementation. This is especially important for women who are pregnant or planning a pregnancy.
The first thing to understand when choosing a supplement is the difference between folic acid and methylfolate. Options for supplementation may include taking a medical food such as Deplin or an OTC multivitamin that contains methylfolate.
Supplementing with a natural form of vitamin B12—as opposed to cyanocobalamin—may also contribute to better health outcomes.
A good place to start is with the Methyl-Life® product range, which has been designed specifically for those with MTHFR gene mutations. This comprehensive range includes clinically tested methylfolate and Vitamin B12, available as separate supplements or as part of multivitamin formulas. Methyl-Life® also offers a variety of other nutrients shown to support cognitive function, energy production, mood, and more.