MTHFR Gene Mutation Symptoms in Adults (and How to Manage Them)

An MTHFR gene mutation results in a deficiency of Methylenetetrahydrofolate-reductase, an enzyme required for folate metabolism. This deficiency can affect various bodily systems and organs, resulting in several symptoms and health conditions.

Some of these symptoms include:

This article will analyze MTHFR gene mutation symptoms in adults, how they are linked to MTHFR, and any related health implications. We will then provide an overview of managing MTHFR symptoms through diet and supplementation.

While many of the symptoms commonly associated with MTHFR are anecdotal, these are said to include:

The MTHFR gene mutation results in a lack of the enzyme required to process folate and B12, both of which are essential for recycling homocysteine. Homocysteine is an amino acid formed in the blood naturally produced during the methylation process.

Deficiency in folate, B12, and B6 results in a buildup of homocysteine in the tissues, which is highly toxic to the vascular walls.

Elevated homocysteine levels have been shown to increase the risk of developing blood clots in the arteries and veins and atherosclerosis (hardening of the arteries). In high levels, homocysteine promotes oxidative stress, endothelial dysfunction, inflammation, fibrosis, and other damage to the blood vessels.

Homocysteine is also shown to impair platelet function and coagulation factors, promoting abnormal platelet activity and blood coagulation. This increases the risk of thrombotic events such as stroke and deep vein thrombosis.

Some research has also linked homocysteine to high blood pressure as it may also cause arteriolar constriction, renal dysfunction, and increased sodium reabsorption, resulting in increased arterial stiffness.

The MTHFR enzyme plays an important role in processing amino acids, specifically, the conversion of homocysteine to methionine. A genetic mutation in the MTHFR gene can lead to impaired function or inactivation of this enzyme, resulting in insufficient folate metabolism. As folate and B12 are also required to process homocysteine, this mutation can result in elevated levels of homocysteine, especially in adults who are already folate-deficient.

Elevated homocysteine (hyperhomocysteinemia) severely damages the walls of the veins and arteries, causing inflammation and vascular remodeling. It can also affect platelet regulation, causing thickening of the blood and a higher risk of thrombotic events.

Numerous studies have shown that hyperhomocysteinemia is linked to vascular disease and several age-related pathologies like Alzheimer’s disease, stroke, and Parkinson’s disease. It has also been implicated in osteoporosis, end-stage renal disease, insulin resistance, aneurysm, hypothyroidism, cancer, and gastrointestinal disorders.

The MTHFR 677C>T polymorphism, particularly, has been linked to birth defects and pregnancy-associated diseases, including miscarriage and other pregnancy complications. However, study results have been conflicting.

Adverse pregnancy outcomes are believed to be due to increased homocysteine, which can damage the placenta resulting in impaired implantation and decreased fetal perfusion. Impaired DNA methylation results in decreased methionine levels, which may be responsible for various perinatal and obstetrical complications as well as complications due to the accumulation of folic acid.

A 2018 meta-analysis found that MTHFR C677T was significantly associated with recurrent pregnancy loss in developing countries but not developed ones.

Previous studies have linked MTHFR to complications such as intrauterine growth restriction, preeclampsia, preterm labor, and ablation placenta.

For offspring, MTHFR may increase the risks of birth defects and long-term deficits in brain development. 

Many studies have shown that the MTHFR 677C>T mutation is a risk factor associated with neural tube defects and other adverse outcomes to fetal development such as spina bifida, congenital heart defects, and malformation of the nervous system.

Estrogen’s effects on the body depend on how it is metabolized. This process occurs primarily in the liver through Phase I (hydroxylation) and Phase II (methylation and glucuronidation).

The methylation of estrogen is driven by the COMT enzyme, a methyltransferase. COMT depends on a methyl group supplied by SAMe, the body’s methyl donor, along with methylfolate and vitamin B12. However, insufficient methylfolate due to the MTHFR gene mutation can impair estrogen detoxification and result in excess estrogen.

Symptoms associated with high estrogen include breast tenderness, nausea, bloating, abdominal cramps, headaches, weight gain, skin hyperpigmentation, hair loss, and abnormal uterine bleeding.

Numerous studies have demonstrated the association between MTHFR and mental health disorders such as depression, anxiety, schizophrenia, and bipolar disorder.

Deficiencies in MTHFR result in increased homocysteine levels, leading to reduced levels of S-adenosylmethionine (SAMe). In the brain, SAMe is required to donate methyl groups to COMT, which is involved in neurotransmitter analysis.

Folate is intimately linked to synthesizing neurotransmitters in the central nervous system, including serotonin, norepinephrine, and dopamine. These neurotransmitters are essential for maintaining a healthy mood.

Low levels of methylfolate and increased homocysteine lead to low levels of monoamine neurotransmitters, which have been found in patients with depression.

The symptoms associated with an MTHFR gene mutation result from the body’s inability to create and maintain sufficient levels of certain nutrients—namely folate, vitamin B12, and SAMe. The downstream effect of these deficiencies affects nearly every system in the body.

Dietary interventions that can help manage MTHFR-related symptoms include eating foods rich in folate and B12.

Foods high in natural folate include leafy greens, brightly-colored fruits, nuts, seeds, peas, beans, grains, dairy, eggs, lean beef, poultry, and seafood. Natural Vitamin B12 is present in animal products such as liver, fish, beef, poultry, eggs, milk, and dairy.

Supplementation, however, is a much more effective means of maintaining nutrient levels. Methylfolate and methylcobalamin have been shown to restore deficiencies more readily than synthetic forms (folic acid and cyanocobalamin) as they are already in their active form. This means the body can absorb and utilize the vitamins immediately.

Methyl-Life® has created a broad range of nutritional supplements to help manage MTHFR symptoms and support overall health. Every product contains the most bioavailable forms of nutrients, including the clinically researched Magnafolate®. Supplement options include methylfolate, active B12, methylated multivitamin formulas, and various other nutrients shown to support cardiovascular health and cognitive function.