MTHFR stands for Methylene-Tetra-Hydro-Folate-Reductase. Some individuals with the homozygous MTHFR mutation have elevated homocysteine levels. Elevated homocysteine levels are a risk factor for blood clots. The individual with the MTHFR mutation who have normal homocysteine levels are not at increased risk for clots. Thus, the MTHFR mutation by itself is not a clotting disorder.

There are 3 scenarios:
a. You do not have the MTHFR mutation (44% of all people),
b. You are heterozygous (1 variant gene) 44% of people are heterozygous, and there are no medical problems being heterozygous
c. You are homozygous (2 variant genes), that happens in 12% of people. It is the homozygous MTFHR that can create problems

Homozygous MTHFR is associated with higher homocysteine levels. However, it is the fasting homocysteine level that counts, independent of whether the patient has the MTHFR mutation or not. If an individual's fasting homocysteine level is normal, there is no need for vitamin B or folate therapy - even if the patient has the homozygous MTHFR mutation.

Researchers have looked at MTHFR gene mutations as being a possible factor in recurrent miscarriages with quite mixed results. Some studies find that MTHFR gene variations increase the risk of miscarriages while others find no link.

Right now, some doctors test for MTHFR in patients with history of miscarriage and offer aggressive treatment to everyone with MTHFR gene mutations. Others do not ever test for MTHFR variants. There is currently no official recommendation and no conclusive evidence about the value of testing for MTHFR gene mutations, so practice varies widely.

Some doctors believe that hereditary thrombophilias, such as Factor V Leiden, may increase the risk of miscarriage by creating tiny blood clots that block nutrient flow to the placenta and so they include MTHFR gene mutations in this category. However, hereditary thrombophilias are not universally accepted as a cause of recurrent miscarriages -- the only thrombophilia disorder with a widely accepted treatment is antiphospholipid syndrome.

Doctors who follow the theory of MTHFR variations as a thrombophilia disorder may prescribe anti-clotting therapy such as heparin and low dose "baby" aspirin to reduce the risk of blood clots. Others may recommend high doses of folic acid and possibly other B vitamins with the idea that this will reduce homocysteine levels and eliminate any added risk on that front.

In doctors who believe in treatment of women with MTHFR gene variations, some believe in treating women who are heterozygous as well as homozygous, whereas others only treat women who are homozygous.

Other doctors do not test for MTHFR gene mutations at all because the link is far from conclusively proven, but they choose to test homocysteine instead and recommend therapies for women with high homocysteine levels.

Still other doctors (and probably the majority fall in this category) do not test for either MTHFR or homocysteine because neither has a formally recommended treatment that is solidly shown to reduce the risk of miscarriage.

A normal homocysteine level is often defined as one being less than 13.0 micromol/L. The higher the level, the higher the risk for clots. Levels can be lowered by taking a multiple vitamin with a high content of folic acid (for example 400 mcg = 0.4 mg), vitamin B6 (= pyridoxine; for example 25 mg) and B12 (= cobalamin; for example 1 mg).
Often folate treatment alone (dose: 0.4-5 mg per day) lowers homocysteine levels into the normal range. However, several publications in the last several years have consistently shown that lowering homocysteine levels does NOT change the risk for future blood clots. Thus, there is at present no good reason to treat an individual with elevated homocysteine levels with vitamin B6, vitamin B12, or folic acid , at least not a person with only slightly or moderately elevated levels (say, levels below 30 micromol/L). Whether individuals with more significantly elevated homocysteine levels may benefit form lowering of homocysteine levels is not know.