Homocysteine, MTHFR and pregnancy: what’s the relationship?

For women who have had recurrent miscarriages or have difficulty getting pregnant, some control tests are prescribed which often include blood homocysteine ​​values ​​​​and the analysis of MTHFR mutations. Let’s see why.

What is homocysteine

It is an amino acid that is formed from methionine, another amino acid that is introduced into the body with food.

Elevated homocysteine ​​levels in the blood have been associated with cardiovascular problems. According to some studies, hyperhomocystinemia also represents a risk factor for  repeated miscarriages (in relation to MTHFR mutations) and for other pregnancy complications.

What are normal homocysteine ​​levels?

Normal values ​​vary with age .

• 0-30 years: 4.6-8.1 µmol/L
• 30-59 years: 6.3-11.2 µmol/L (males); 4-5-7.9 µmol/L (females)
• Age >59 years: 5.8-11.9 µmol/L

The higher the homocysteine ​​level in the blood, the higher the risk of clots forming.

Since a deficiency of folic acid, vitamins B6 and B 12 can cause an increase in homocysteine ​​in the blood, levels can be lowered by taking a multivitamin with a high folic acid content (e.g. 400 mcg = 0.4 mg), vitamin B6 (= pyridoxine, e.g. 25 mg) and B12 (= cobalamin, e.g. 1 mg).

MTHFR mutations

MTHFR is a gene that codes for an enzyme: 5,10- methylenetetrahydrofolate reductase . The MTHFR C677T mutation or, more rarely, MTHFR 1298C  in the homozygous form, can be associated with an increase in homocysteine ​​levels in the blood.

The MTHFR C677T mutation would also represent a risk factor for spina bifida, for pregnancy complications such as preeclampsia, recurrent spontaneous abortions, decreased birth weight of newborns, lower placenta weight at birth.

If the mutation is heterozygous, there appear to be no major implications, while if the mutation is homozygous and homocysteine ​​levels are normal, there would be no increased risk of complications.

It is an area in which studies follow one another and which often have conflicting results, for this reason there is no common line of therapy (except for the recommendation to take a folic acid supplement which is universal).

How to counteract the increase in homocysteine ​​levels?

Usually a woman who discovers that she has high homocysteine ​​levels is a woman who is trying to get pregnant or who has a history of recurring miscarriages.

Since pregnancy usually involves a slight reduction in homocysteine ​​in the blood, this is yet another reason to take folic acid during pregnancy. In the event of an MTHFR mutation, however, it is preferable to take a specific formulation of folic acid which we will explain below.

The studies are not all aligned and agree on the role of hyperhomocysteinemia and the MTHFR mutation in recurrent miscarriages, and therefore also the therapies prescribed by the gynecologist can vary greatly.

Doctors who deem MTHFR mutations to be a thrombophilic disorder may prescribe anti-clotting therapy consisting of heparin and aspirin (or aspirin) to reduce the risk of blood clots. Others prescribe high doses of folate and possibly other B vitamins to reduce blood homocysteine ​​levels and thereby reduce the risk of miscarriage.

There are doctors who evaluate treatments only in the case of homozygous mutations of the MTHFR gene and others who prescribe therapy even when the mutation is heterozygous.

Other doctors do not test for mutations in the MTHFR gene because they do not consider it a reliable parameter and prefer to test only homocysteine ​​and in the case of high values ​​of the latter, they prescribe a therapy to lower it.

Finally, other doctors still don’t test for MTHFR or homocysteine.

Who is right? We will know with time and with the increase of studies.

Surely folate supplementation must never be lacking in anyone seeking a pregnancy, there is no doubt about this.

Which folic acid in case of MHTFR mutations

If there is an MTHFR mutation, normal folic acid supplementation is not enough. In these cases, but also in the event of an important deficiency, there are formulations to be taken which favor the bioavailability and consequently the absorption of the nutritive principle.

Folic acid is the man-made form of folate. Folate is a B vitamin naturally found in some foods. It is necessary to form healthy cells, especially red blood cells and in pregnancy to prevent neural tube malformations.

Vitamin supplements and vitamin-fortified foods contain folic acid.

The formulations that make folic acid more bioavailable to our body in case of MTHFR mutations are L-methylfolate and methyltetrahydrofolate.