Everybody has the gene 5-methyltetrahydrofolate reductase, which is also known as MTHFR.
MTHFR is an enzyme that plays a key role in the metabolism of folate, a B group-vitamin essential for many bodily functions such as DNA synthesis and repair, proper cell division, and the production of red blood cells.
The MTHFR gene is responsible for converting the type of folate we consume to create the type of folate our body uses. A lack of this usable folate can result in some health conditions and disorders. A malfunctioning less functional variation of the MTHFR gene can lead to lower levels of usable folate and add to this risk. You can be tested for the MHFR gene variation but this testing is not routine despite that it is also not uncommon to test positive to this malfunction. These gene changes can result in a reduction from 100% activity to between 86% all the way to 18% activity depending on the gene variation. A positive test can mean you are susceptible to a number of risks, including recurrent pregnancy lost and early stage miscarriages.
Whilst there is no cure for these MTHFR gene variations, there are very straight forward approaches with monitoring essential that you can undertake to support your pregnancy journey and reduce the risk of miscarriage, pre-eclampsia or your future child’s genetics.
Demeter Fertility manages patients with MTHFR variations with different approaches depending on the symptoms, test results and outcomes associated with the diagnosis and your treatment.
So, finding out that you have an unhelpful MTHFR polymorphism, isn’t the end of the world. Check your homocysteine and get onto the right supplement for you. Remember this super important note! It’s not just the presence of the gene, it’s also the variation of the gene, and the exposure in a person’s lifestyle that determines any potential effect on how well your cells are working.
How can I prevent a positive MTHFR test?
It is not possible to prevent testing positive to an MTHFR mutation as it is a genetic variation in your DNA. This is inherited from your parents.
How do I know if I’m at risk of a positive MTHFR test?
You may be at risk if you’ve had:
- recurrent pregnancy losses
- had multiple miscarriages
- have a family history of mutated MTHFR gene
- had genetic issues with another pregnancy
What are my treatment options if I have an MTHFR mutation?
Treatment options will depend on the specific gene variation, enzyme activity, homocysteine levels, dietary habit and the symptoms or health problems that are present. Some possible treatment options include:
- Eating a healthy diet: Eating a diet rich in folate-containing foods such as leafy green vegetables, fortified cereals, and legumes can help support the body's methylation process.
- Avoiding alcohol: Alcohol can interfere with the methylation process and increase the risk of health problems.
- Vitamin and mineral supplements, such as folate, vitamin B6, and vitamin B12 in appropriate doses (which will generally be person specific). High homocysteine levels may require betaine, riboflavin, or methionine to complement lower homocysteine levels.
- Monitoring: Regular monitoring of homocysteine levels, and other related biomarkers such as folate, B12, and red blood cells, may be recommended to track the progress of the treatment.
- Maintaining a healthy lifestyle: Maintaining a healthy lifestyle through regular exercise, stress management, and getting enough sleep can also help lower your risk of health problems related to an MTHFR variation.
- Monitoring Homocysteine levels to assess treatment progress.
- Genetic counseling: In people with severe variations and when planning to have children, genetic counseling may be helpful to help understand the risks of passing on the MTHFR mutation.
It's important to note that not all people with an MTHFR mutation will require treatment, and in many cases, a healthy diet and lifestyle is enough to manage the condition.
What other risks are associated with MTHFR in pregnancy?
During pregnancy, women with an MTHFR gene variation may have a higher risk for miscarriages, preeclampsia or birth defects, such as spina bifida.
What are the potential health effects of having an MTHFR variation?
Some of the potential health effects include:
- Elevated levels of homocysteine: Homocysteine is an amino acid used as part of folate metabolism. High levels are a risk factor for heart disease and blood clots.
- Neural tube defects: Folate plays a crucial role in the development of the neural tube in a developing fetus, and MTHFR mutations can increase the risk of neural tube defects such as spina bifida.
- Risk of miscarriage and infertility: MTHFR mutations may also be associated with an increased risk of miscarriage and infertility.
- Increased risk of cancer: Some studies suggest that MTHFR mutations may be associated with an increased risk of certain types of cancer, such as colon, lung, and breast cancer.
- Cognitive and behavioural problems: High levels of homocysteine are associated with increase risk of mental health problems including depression, anxiety, and autism.
What is folate and what does it do?
Folate is a B-vitamin that is naturally present in many foods. Folate helps to form DNA and RNA and is involved in making proteins. Your body also needs folate for your cells to divide. It plays a key role in breaking down homocysteine, an amino acid that can exert harmful effects in the body if it is present in high amounts.
Folate is also needed to produce healthy red blood cells and is critical during periods of rapid growth, such as during pregnancy and foetal development. A form of folate, called folic acid, is used in fortified foods and most dietary supplements. Folate is naturally present in many foods, and folic acid is added to some foods.
How can I raise my folate intake?
Folate is naturally present in:
- Beef liver
- Vegetables especially asparagus, brussel sprouts, and dark green leafy vegetables such as spinach
- Nuts, beans, and peas (such as peanuts, black-eyed peas, and kidney beans)
Folic acid is added to the following foods:
- Enriched bread, flour, cornmeal, pasta, and rice
- Fortified breakfast cereals
Folate is available in multivitamins and prenatal vitamins. It is also available in B-complex dietary supplements and supplements containing only folate. In dietary supplements, folate is usually in the form of folic acid, but 5-MTHF (methylfolate or 5-methyltetrahydrofolate in its long chemical name) is also used.
How do I know I’m getting enough folate?
This is an interesting question, as most people have normal folate levels. However there is a particular amino acid called homocysteine, and this is a good test to see if your genetics are being balanced by your lifestyle. The MTHFR gene has an important role here. Someone with a mix of polymorphisms above may have a high homocysteine level.
High homocysteine levels are associated with high blood pressure, heart failure, stroke, Alzheimers Disease, elevated cholesterol levels, type II diabetes mellitus, increased inflammatory state, kidney failure, psoriasis, depression and other mental illnesses, migraine and headache, auditory and optical disorders including macular degeneration, recurrent miscarriage, infertility, neural tube defect and Autism Spectrum Disorder, amongst others.
Most people in Australia get enough folate. However, certain people are more likely than others to have trouble getting enough folate:
- Females aged 14–30 years
- People with alcohol use disorder
- People with disorders that lower nutrient absorption (such as celiac disease and inflammatory bowel disease)
- People with an MTHFR gene variant
What are some effects of elevated Homocysteine on reproductive health and fertility?
Folate deficiency and homocysteine are important for egg quality and maturation, implantation, placental development and growth, foetal growth, and organ development. Low folate and/or high homocysteine levels correlate with subfertility.
Increased levels of homocysteine during pregnancy is associated with placental vascular damage and may be correlated with miscarriage, pre-eclampsia or other unfavourable outcomes such as gestational diabetes and preterm delivery. Homocysteine levels are a marker for pregnancy-induced hypertension and an up to 10 times increased risk of stroke in pregnancy.
Folate deficiency and increased levels of homocysteine are associated with Neural Tube Defects (NTDs) such as spina bifida. A high frequency of MTHFR polymorphisms has been found in mothers with foetuses affected by neural tube defects and cardiac malformations.
Folate supplements reduce the risk of delivering newborns affected by autism spectrum disorders and improve children's language competency. High homocysteine levels in early pregnancy can increase the risk of developing severe preeclampsia, and supplementation of multivitamins containing folic acid in the second trimester is associated with its reduction. Furthermore, homocysteine levels are inversely related to insulin sensitivity in preeclampsia, a good thing. When the plasma homocysteine level rises to >10 μmol/L in early pregnancy, the risk of developing severe preeclampsia has been shown to be more than 50%.
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