Methylenetetrahydrofolate reductase (MTHFR) deficiency is a genetic condition affecting how the body processes folate, a B vitamin essential for functions like DNA synthesis and repair.
What is MTHFR Deficiency?
The MTHFR enzyme facilitates a specific step in the body’s methylation cycle. This complex biochemical process occurring billions of times per second within cells influences detoxification, immune function, and energy production. The MTHFR enzyme’s primary role is to convert 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate (5-MTHF), the active form of folate the body can readily use.
When the MTHFR enzyme is deficient or its activity is reduced, the body’s ability to convert folate into its active form is impaired. Consequently, homocysteine, an amino acid, may accumulate in the bloodstream, as 5-MTHF is necessary for its conversion into methionine. Elevated homocysteine levels are known as hyperhomocysteinemia.
How MTHFR Deficiency Develops
MTHFR deficiency stems from genetic variations in the MTHFR gene. Everyone inherits two copies of this gene, one from each parent. These genetic changes, often called polymorphisms due to their commonality, can lead to a less efficient MTHFR enzyme.
The two most studied genetic variants are C677T and A1298C. The C677T variant results in an enzyme that is less active, and individuals with two copies (homozygous, or TT genotype) have higher homocysteine and lower serum folate levels. While the A1298C variant alone may not significantly affect folate processing, having one copy of C677T and one copy of A1298C (compound heterozygous) can result in effects similar to those seen in individuals homozygous for the C677T variant. A child inherits this autosomal recessive condition if they receive a faulty gene copy from both parents.
Recognizing the Health Impacts
High homocysteine levels have been linked to an increased risk of cardiovascular issues like atherosclerosis (hardening of the arteries) and blood clots. However, some research suggests that the direct link between MTHFR variants and cardiovascular disease or thrombosis is not definitively established.
The deficiency may also affect neurological and mental health due to folate’s role in neurotransmitter synthesis. Low folate levels can lead to abnormal levels of neurotransmitters like serotonin and dopamine, potentially contributing to conditions like depression, anxiety, and cognitive issues like brain fog. Some studies suggest a link between MTHFR variants and conditions like ADHD, autism spectrum disorder, bipolar disorder, and schizophrenia.
During pregnancy, MTHFR deficiency and associated high homocysteine levels may increase the risk of complications like neural tube defects (e.g., spina bifida, anencephaly) in offspring, and recurrent miscarriages. While some studies show a correlation, the overall risk of neural tube defects remains low, especially with adequate folic acid intake. Other symptoms associated with MTHFR deficiency include chronic fatigue, muscle pain, and headaches. The severity and manifestation of symptoms vary widely, and many individuals with MTHFR variants may not experience significant health problems.
Diagnosis and Management
Diagnosing MTHFR deficiency involves blood tests to measure homocysteine and folate levels. High homocysteine levels coupled with low methionine levels can indicate the condition. Genetic testing is available to identify specific MTHFR gene variants like C677T and A1298C.
Management strategies involve dietary adjustments and supplementation. Consuming natural folate from foods like leafy green vegetables, legumes, and lean proteins is recommended. Individuals with MTHFR deficiency are advised to avoid synthetic folic acid, which is found in many fortified foods and supplements, as their bodies may struggle to process it efficiently, potentially leading to its accumulation.
Supplementation with methylfolate (5-MTHF), the active form of folate, is emphasized as it bypasses the conversion step that the MTHFR enzyme performs. Other B vitamins like methylcobalamin (B12) and B6 may be recommended to support homocysteine metabolism. Lifestyle adjustments, including stress management, contribute to overall well-being. Consulting a healthcare professional for a precise diagnosis and a personalized management plan is important, as self-treatment can be harmful.