MTHFR (full name: 5,10-methylenetetrahydrofolate reductase) is a much-discussed enzyme. The implications of abnormal MTHFR enzyme activity are the subject of considerable debate. Abnormal activity of this enzyme is not unusual and affects roughly half of all people.
One of the functions of the enzyme MTHFR is to make the biologically active form of folate (5-MTHF) available from 5,10-MTHF. Both folates play an important role in the formation of nucleotides, the building blocks of genetic material. This takes place through a complex chain of reactions involving a number of different enzymes and cofactors (such as vitamins B2, B3, B6, B9, B12 and zinc).
An abnormal MTHFR function can also inhibit the metabolisation of the toxic metabolite homocysteine into the amino acid methionine, as 5-MTHF is required for this process. If the concentration of homocysteine is and remains too high, this can lead to health problems.
However, an increase in the homocysteine level can also be caused by a deficiency of folate, vitamin B2, vitamin B6, vitamin B12 or betaine, or by an abnormal function of the enzyme methionine synthase (MTR). In practice, a slightly reduced MTHFR function alone will not therefore quickly lead to insufficient quantities of 5-MTHF.
The enzyme MTHFR does not directly influence the metabolisation of drugs. However, there are drugs that, just like the enzyme MTHFR, have an impact on folic acid metabolism. A well-known example is methotrexate, a drug used to treat rheumatism and, in higher doses, as an anticancer drug. However, there is no active dose management with regard to MTHFR enzyme activity and methotrexate.
Genetic predisposition
The activity of the enzyme MTHFR varies from one individual to another.
There are two known, common variations in the MTHFR gene that can result in reduced activity of the MTHFR enzyme. In practice, the impact of a slightly reduced MTHFR function only is low and will not quickly lead to health problems.
The principal variation of which we are aware is C677T (rs1801133 G>A).
This can occur in homozygous (AA) and heterozygous (GA) form. In the first case enzyme activity is reduced to 30% of its normal level and in the second case to 65% of its normal level.
Another possible variation is A1298C (rs1801131 T>G). This has less of an effect on enzyme activity. Even in the case of the homozygous variant (GG) there is still around 60% of normal enzyme activity.