The body has to turn folates from food, and folic acid, into forms it can use. This job is done by enzymes. Sometimes, the gene ‘code’ for an enzyme differs from one person to another. These ‘gene variants’, can produce enzymes that have slightly different forms. This information is about one of these enzymes, MTHFR, and the gene that makes it. MTHFR changes one form of natural folate, but not folic acid, into another natural form. Folic acid is not usable until it is changed into a natural form, but this is done by a different enzyme, DHFR.
Shine understands that some people have become worried by what they’ve read on certain websites about MTHFR variants, and don’t know whether they should have their genes tested, or avoid foods which have folic acid added. Shine has taken guidance from one of the world’s leading experts in this field, Prof Anne Molloy. This is a summary of her advice.
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Here’s some more detail about this for those particularly interested in this subject
MTHFR (methylenetetrahydrofolate reductase) is an enzyme involved in the body’s use of natural folate. It converts 5,10 methylenetetrahydrofolate to 5-methyltetrahydrofolate (methyl folate), one of the main forms of folate in the blood circulation and an important form of folate used by the body. There is one well-known common genetic change that results in a version of enzyme that works less well under certain conditions.
How common are MTHFR variants?
The well-described common variant is 677C>T where the C form is most common and the T form is the rarer version that produces an enzyme with poorer function. Every gene has two copies, so an individual can have a CC genotype, a CT genotype or a TT genotype. In the UK, around 12% of the population have a ‘double’ copy of the less usual gene (homozygous for TT). Having two TT copies affects people more than having one C and one T copy (heterozygous). Other variants have been discovered in the MTHFR gene, for example a 1298A>C variant, but this is closely linked to 677C>T and there is no evidence that it has an independent effect beyond its association with 677C>T.
What are the effects of these variants?
The MTHFR 677TT gene variant can result in a version of the enzyme that works less well under certain conditions. For example, the 677TT enzyme is less stable, and works less well when blood folates are low. This can lead to even lower blood folate levels than could be expected from looking at intake. It also means homocysteine can build up, which is associated with several health issues. However, it is important to note that this variant does not result in a completely blocked enzyme and adding more folate to your diet helps to stabilize the enzyme and make it function better.
How does it affect the way the body handles folic acid rather than natural folates?
It doesn’t. Folic acid is changed into the body’s primary usable form of folate, tetrahydrofolate (THF), by a different enzyme, Dihydrofolate Reductase (DHFR). Folic acid has been shown in clinical trials to raise folate levels and help prevent NTDs. Shine advises beginning to take supplements containing 400mcg of folic acid for three months before stopping contraception, with 2.5mcg of B12 per day.
What is methyl folate? How is it different to folic acid?
Methyl folate is the biologically active form of folate formed when MTHFR acts on natural 5,10 methylenetetrahydrofolate, within the body. The next step in the body’s use of methyl folate is to convert it to the primary usable form, THF, through an enzyme that requires vitamin B12. Thus, methyl folate is a natural source of THF, as long as vitamin B12 is available. It can be taken as a supplement, which can bypass any potential blockage caused by reduced MTHFR activity.
Can I take methyl folate instead of folic acid?
The important thing is to increase your intake of folate well before you conceive whichever form you choose. Methyl folate is generally more expensive than folic acid, and you will need to be sure to take a supplement of B12, at least 2.5mcg per day as well, as B12 deficiency would prevent methyl folate working as well as it should. However, it is worth remembering that the clinical trials of folic acid in prevention of NTDs proved folic acid was effective.
Do I need to have genetic testing for MTHFR variants?
No. If you are very concerned, you could have your serum or red cell folate and your vitamin B12 checked before trying for a baby. But in general, there is no advantage to having your MTHFR genes tested, since having a good folate status will help to optimize the function of the MTHFR TT gene in any case.
With many thanks to Professor Anne Molloy, Trinity College Dublin, for her kind assistance