Selected Notes on MTHFR

UPDATE- Please visit the MTHFR website by clicking HERE.

It will provide you with answers to your many questions about MTHFR.

MTHFR - stands for Methylenetetrahydrofolate Reductase (the enzyme is in a mutated form when talking about it in these specific cases) - Not that you`ll ever really need to know that.

"MTHFR is a common genetic variant that causes a key enzyme in the body to function at lower than normal rate. This can lead to a variety of medical problems, when people with MTHFR are exposed to more toxins than their bodies can handle. There are over 50 known MTHFR variants, but the two prime variants are called 677 and 1298, the numbers refer to their location on the gene. The routine lab test for MTHFR variant only reports on 677 and 1298 as these are the most studied.

"The 677 variant is associated with early heart disease and stroke and the 1298 variant with a variety chronic illnesses. The MTHFR is reported out as heterozygous or homozygous. If you are heterozygous that means you have affected gene and one normal gene. The MTHFR enzyme will run at about 55% to 70% efficiency compared to a normal MTHFR enzyme. If you are homozygous then enzyme efficiency drops down to 7% to 10% of normal, which of course makes a huge difference."

"The worst combination is 677/1298 in which you are heterozygous to both anomalies. Many chronic illnesses are linked to this anomaly. 98% of autistic children have an MTHFR anomaly. Fibromyalgia, irritable bowel syndrome, migraines, are all conditions associated with MTHFR anomaly."

"MTHFR can make you susceptible to illness because the pathway is the primary source of glutathione production in the body. Glutathione is the body's primary antioxidant and detoxifier. People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxins."

"As we age MTHFR problems get much worse due to the accumulation of toxins and the cumulative effect of oxidative stress, which ages our bodies."


Non mutated MTHFR is one of the leading regulatory enzymes of homocysteine metabolism. Homocysteine metabolism is an extremely important factor of our metabolic systems. This process touches many aspects of our general health and is therefore very important.

The MTHFR Mutation is a defective enzyme that hinders this process. The mutation of the MTHFR gene is directly related to hyperhomocysteinemia (high or elevated levels of homocysteine).

High levels of homocysteine can be attributed to many conditions such as:

The condition can lead to high rates of dementia /Alzheimer`s due to a decrease in vitamin B-12.

High homocysteinemia can lead to coronary artery disease, common carotid atherosclerosis other Vascular Diseases.

Complications in Pregnancy Due To Neural Tube Defects.


Rheumatoid Arthritis

Downs Syndrome



Neuropsychiatric Disorders

Non Insulin Dependant Diabetes

Early Pregnancy Loss

Spontaneous Abortion (Viable Fetus)

Placental Abruption, Low Birth Weight

Other Conditions

MTHFR mutation can be homozygous (2 copies) or heterozygous (1 copy), with more people being heterozygous and carrying only one MTHFR mutated gene. Compound heterozygous (one copy of each mutation). Homozygous, of course, can cause more issues and become more serious.

It`s a fairly easy thing to test for by checking homocysteine levels in the blood.

Treatment consists of simple vitamin supplements --- FolaPro L-methyl tetrahydrofolate by Metagenics, OR, 5 tetrahydrofolate or methyl folate.

Longevity Plus, H.R. T. Plus with 5-tetrahydrofolate.

Life Extension, optimized folate (5-MTHF).

OR prescriptions like:

*Deplin/ 7.5 mg l-methylfolate


*Metanx-L methyl folate calcium (as Metafolin) 3 mg, Pyridoxal 5` phosphate 35 mg, methylcobalamin 2 mg.


Methyl B-12 injections

The vitamin supplementation is lifelong. After childbirth you may switch from prenatal to a women`s multivitamin.

See a specialist to discuss whether you are a candidate for Lovenox. Also, you may consider having a FULL antiphospholipid antibodies panel run.

Many MTHFR patients also have Antiphospholipid Syndrome. If you have both, you are a likely candidate for Lovenox (injections of low molecular weight heparin) throughout a pregnancy to prevent clotting.

MTHFR mutations interfere with the body`s ability to absorb folic acid. Folic acid deficiencies for babies can cause neural tube defects like spina bifida.

In addition, lack of folic acid can cause clotting-related problems. Since the teeniest, tiniest blood vessels are in the uterus, a female can have microscopic clots that don`t harm them, but cut off the blood supply to the embryo/fetus. This can cause implantation problems, m/c, or even stillbirth. So properly treating your MTHFR is critical.

MTHFR is one of several different kinds of inherited thrombophilia. (Antiphospholipid Syndrome is acquired thrombophilia.)

Please be sure to have your parents and siblings tested for MTHFR mutations as well. If positive, then they should discuss taking baby aspirin and additional Folgard as well (one Folgard per mutation.)

During pregnancy adding extra folic acid is suggested beyond the 800 mg.

Children will need a children`s multivitamin and later extra folic acid, too.

There is controversy as to the importance of homocysteine levels when it comes to MTHFR mutations.

MTHFR causes folic acid deficiency, which causes elevated homocysteine levels, which causes clotting problems, which causes infertility or miscarriage.

MTHFR causes folic acid deficiency, which causes clotting problems, which causes infertility or miscarriage which may or may not cause elevated homocysteine levels.

Homocysteine levels may be checked. Homocysteine levels (particularly in young women) are not an accurate predictor of clotting troubles.

Baby aspirin is a blood thinner (relatively mild). Lovenox (low molecular weight heparin) is an anticoagulant (slows clotting.) They have two very different functions in the body. Your doctor may or may not want you to use both.

AVOID Laughing gas/Nitrous Oxide - Nitrous oxide uses up vitamin B-12 can cause severe problems or death in people with MTHFR Disorder.

AVOID Bactrim DS- In pregnancy it is associated with increased incidence of cleft lip. Otherwise the system is depleted of Vitamin B-12.

AVOID SamE, an over the counter product as this S-adenosyl-methionine can further inhibit MTHFR.

C77TT is associated with an increase risk of esophageal cancer.

MTHFR Disorder is associated with an increased risk for postmenopausal breast cancer, schizophrenia, anxiety, bipolar disorder, migraines, and strokes.

It effects of seizures and medications used to treat them.

There is a reduced risk of non-Hodgkins lymphoma and acute lymphocytic leukemia in adults.



Also known as: MTHFR DNA testing

Formal name: Methylenetetrahydrofolate Reductase Mutations, C677T and A1298C

Related tests: Homocysteine, Factor V Leiden Mutation and PT 20210 Mutation, Vitamin B12 & Folate, Cardiac Risk Assessment, Methotrexate


British Journal of Haematology Volume 105 Issue 1, Pages 98 - 101

2009 Blackwell Publishing Ltd

The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss.

We have investigated the potency of the C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene as a genetic risk factor in women with a history of early (12 weeks gestation) and/or late (>12 weeks gestation) recurrent miscarriage (three or more consecutive pregnancy losses). Fifty-seven of the total 173 (32.9%) patients were heterozygous for the MTHFR mutation, 14/173 (8.1%) were homozygous (allele frequency 0.25).

The prevalence of the MTHFR mutation in these women did not differ significantly from that in the control group of parous women with uneventful pregnancies, where 30/67 (44.8%) were heterozygous and 6/67 (9.0%) homozygous for the mutation (allele frequency 0.31; odds ratio for homozygous T/T 0.90, 95% CI 0.30.4). There was no association between the trimester of pregnancy loss and MTHFR genotype. We conclude that the C677T MTHFR mutation is not a risk predictor in women with a history of early or late recurrent miscarriage.

MTHFR disorder Most serious mutation to less serious:

C677T/C677T - Homozygous. Genetic counseling is recommended.

A1298C/A1298C - Homozygous. Genetic counseling is recommended.

C677T/A1298C- Compound heterozygous

C677T- Heterozygous

A1298C- Heterozygous

Immunocompromised individuals are at increased risk for adverse effects.