Folate is a vitamin needed for complicated cellular functioning, deficiency causes diarrhoea, anaemia, poor growth, glossitis, gut lesions and increases the risk of neural tube defects in pregnancy.The MTHFR gene is responsible for an enzyme ( methylenetetrahydrofolate reductase) MTHFR  production. The enzyme is involved in the conversion of the primary form of circulating precursor  in the blood to a form of folate that is able to assist several reactions in the cellular system by adding methyl.

Genetic testing for two common polymorphisms in the gene is being ordered by GPs, alternative practitioners and promoted through some pharmacies. A polymorphism is a variant within a gene that does not necessarily affect its function, unlike a mutation.  There is a large amount of varied, conflicting data reported on these polymorphisms and their associations with many conditions such as autism, schizophrenia, cardiac disease, foetal neural tube defects, poor pregnancy outcomes, infertility and colorectal cancer.

There are two main MTHFR polymorphisms, in the general population 60-70% of individuals will have at least one of the variants, leading to a mild reduction in enzyme production , 10% of the population will be homozygous for these two polymorphisms. The remaining combinations of variants result in varying reductions in the enzyme production.

The current recommendations for clinical practice state that,  although folate is vital for cellular health  and the MTHFR gene has an important role in the folate pathway, there is no statistically significant evidence that the common polymorphisms found on gene testing have a clinical important impact on the pathway. These polymorphisms are common in the general population.  There is no substantial evidence to support the use of MTHFR gene testing in clinical practice as knowledge of the status of the gene is unlikely to change management.

MTHFR status does not alter the recommendation that women who are planning a pregnancy or those in the first trimester of pregnancy take folic acid supplements to reduce the risk of neural tube defects. Taking folic acid before and during pregnancy decreases the risk, just as it does in women who do not have the variants.

There is a lack of strong scientific evidence to show that having one or both MTHFR gene variants causes particular health problems

There are no evidence-based treatments that will improve the health of a patient with one of the gene variants.

Many genetic service providers have stopped accepting referrals for consultations in relation to MTHFR given the lack of clinical usefulness of the test in management guidelines .

There is an association between the presence of MTHFR gene variants and increased homocysteine levels: however

.- high homocysteine was once thought to increase risk of blood clots, cardiovascular disease and recurrent miscarriage, recent studies have disproved this theory

- many other factors also increase homocysteine ( diet, lifestyle, other gene variants0. A persons risk of disease can be reduced by following a healthy, balanced diet and avoiding well proven risk factors such as smoking and being overweight

- having a biochemical test for homocysteine levels may lead to more useful information than having the MTHFR gene test ( it is not covered by the Medicare benefits Scheme)

Resources: Centre For Genetics Education, Fact sheet 64: MTHFR gene tests for patients,

The Royal College of General Practitioners, Appropriate diagnostic testing: Patient information,


<- Back to: News