MTHFR genetic variation

If you suffer from depression or mental illness, heart disease, have a history of miscarriage or birth defects, and have a family history of the same, this article may apply to you.

MTHFR Genetic Variation and Health Implications

Inexpensive genetic testing is now available through a simple blood test for the mutation affecting the methylenetetrahydrofolate reductase (MTHFR for short) gene.

People who have MTHFR mutations may have low or high folate levels on blood tests.

Signs of activated folate deficiency may include:

·         Macrocytic anemia

·         Fatigue

·         Irritability

·         Peripheral neuropathy

·         Restless leg syndrome

·         Diarrhea

·         Weight loss

·         Insomnia

·         Depression

·         Psychiatric disorders

Each person receives copies of genes for MTHFR from both their mother and father.  The test enables us to determine whether the genes that affecting the MTHFR involve a "mutation" or are of the "normal" variation. Mutations are not rare.  The most common MTHFR mutation, C677T, is present in the homozygous state (two mutated copies) in 5-10% of the general Caucasian population.   The frequency of the other mutation, A1298C, is reported to be as high as 30% in the general Caucasian population.

Having this gene mutation means that the body doesn't convert as much dietary folate, also called folic acid in supplements, to 5-Methylfolate, the active form that the body can use. Folate is a B vitamin that is essential for many processes in the body that include fighting cancer, making neurotransmitters (like serotonin), making healthy babies (fights miscarriage and birth defects) and lowering homocysteine, a protein that increases risk of stroke or ischemic heart disease.
People with MTHFR mutations tend to have higher rates of cardiovascular disease, but also have more mental health issues, especially depression, and more frequent miscarriages and birth defects. The C677T mutation is associated with Major Depressive Disorder (MDD).  Low folate blood levels have been associated with a poorer response to treatment with antidepressants.

MTHFR variants may also have an effect on cancer risk, though specifics are less clear. The MTHFR variation increases the likelihood of breast cancer and many other cancers that include non-Hodgkin's lymphoma, multiple myeloma, and oral cancer. However, the gene variation actually protects against colon cancer and improves the survival rates from breast cancer, so it's not all bad, as tends to be the case with common gene variants. If a person has one copy of the gene (heterozygous), it generally causes fewer problems than if the person has two (homozygous).
The good news is that most of the ill effects can be overcome with a daily dose of the activated form of folate, called methylfolate, L-methylfolate, 5-methylfolate, 5-MTHF, or by prescription, Deplin. It's generally given in high doses to those who have the variation, which might not be advisable if a person does not have this variation. A person who is homozygous usually needs higher supplementation than someone who is heterozygous. It also means that a high amount of dietary folate is especially important - found in fresh veggies, and fruits, and especially high in leafy greens. But in some cases, vegetables aren't really enough.
Patients who have the MTHFR mutation may find that taking a B complex with methylfolate makes a marked difference in energy, the ability to focus and remember, and may lower anxiety and depression.

Research on this area of research is rather new, and genetic medicine and interpretation is a complicated, and controversial field. It is clear that adequate active folate supports cardiovascular, neural and emotional health.  In addition, it promotes cancer prevention.  If you suspect you might have a MTHFR mutation, if you have a personal and family history of depression, if you have had a poor response to antidepressant therapy, or if you have a history of high homocysteine, it may be worth asking your doctor about testing.

Julie Brush, ND