You’re taking your Folic Acid supplements regularly so you don’t need to worry about getting Folate from your diet. Right? Well… the availability of the right form of Folate may affect hormone balance, implantation, mood, miscarriage, pre-eclampsia and pre-term birth risk in some people.
Here’s what you need to know.
1. We need Methylfolate - which is the active form our body can use
Folic Acid is the synthetic form which is in most supplements
Folate is the natural form found in food
Both Folic Acid and Folate are converted to Methylfolate in the body
Some people have less of the active enzyme needed for the conversion – this is because of a genetic variation called the MTHFR variant (scroll down for the technical bit)
We can get Methylfolate from food
2. Methylfolate levels may affect fertility
PCOS – A methylfolate supplement combination showed more improvement in menstrual cycle regularity, BMI reduction, testosterone and homocysteine reduction and insulin sensitivity. The recent Italian study compared treatment with combined myo-inositol, gymnemic acid and methylfolate to treatment with myo-inositol plus folic acid in women with PCOS.
The MTHFR variant - Approximately 10% of the UK have a genetic variation called homozygous C677T which means they can’t make methylfolate so efficiently. This has been associated with recurrent implantation failure, low mood, higher homocysteine which may affect DNA quality, higher miscarriage risk and pre-eclampsia.
Recurrent implantation failure rates were higher in women with the variant in a Korean review study
High homocysteine - Last year a French study found that infertile couples with the variant had higher homocysteine levels - but this reduced with 600mcg methylfolate supplements daily – the study suggests that people with the variant should be treated with methylfolate instead of high dose folic acid
Methylfolate may also affect mood while trying to conceive and during pregnancy - In February a study found that a prenatal supplement containing methyfolate offered some protective effect against depression in women who had a previous diagnosis of depression.
3. Methylfolate levels may affect pregnancy and miscarriage risk
Miscarriage – 16 women with MTHFR variations and a history of 3 or more miscarriages were given high dose Methylfolate 5mg daily plus B6 50mg daily and B12 1mg weekly resulting in reduced homocysteine levels and 7 live births
Pre-term birth - Recent reviews have found an association between the C677T variant and preterm birth and low birth weight (Wu et al. 2017) (Fang et al. 2018) though not all previous studies demonstrate this.
4. Food contains both folate and methylfolate
‘eating the rainbow’ helps methylfolate levels - rich sources include
green leafy vegetables, spinach, kale, cabbage, broccoli, cauliflower, asparagus, lettuce, peas - vegetables are best lightly cooked or raw
strawberries, blueberries and other berries - including frozen
oranges, grapefruits and citrus fruits - including juices
beans and pulses are rich sources of folate but this is not in the methylfolate form unless they are sprouted
5. Folic acid is important! - and expert opinions vary on the best form of folate
Folic acid is the most cost effective and available way of reducing birth defects. It protects against neural tube defects and supplementing is an important part of prenatal care. For most people it is the cheapest way of providing essential folate supplementation during pre-conception and pregnancy.
The UK government is currently consulting on fortifying bread and flour with folic acid to help prevent neural tube defects and confer other health benefits. A 2015 study estimates that 2000 fewer neural tube defect pregnancies would have occurred since 1998 if the UK had adopted the same policy as the USA in fortifying flour with folic acid.
Red blood cell folate was below the protective level for birth defects in 91% of women of childbearing age in a National Diet and Nutrition Survey
Start taking extra folate before trying to conceive - 3 months is ideal
Not everyone agrees that methylfolate may be a better treatment
Professor Anne Molloy states that maintaining good levels of folate with Folic Acid supplements helps people with the MTFHR variant and that MTHFR testing is not necessary
A study published in May found that when infertile men with the MTHFR variant took 800mcg of folic acid for 3 months their sperm quality, DNA fragmentation and pregnancy outcome improved
6. You need vitamins B12 B6 and B2 to help your body use folate
Taking folate as part of a prenatal that contains other B vitamins is better than taking it on its own. The other B vitamins help you utilise folate and help keep homocysteine low
7. The MTHFR variant – how to get tested
If you have a history of recurrent miscarriage or a diagnosis of unexplained infertility it may be worth getting tested, though maintaining a good intake of folate and other B vitamins through both diet and supplements is the first essential.
Your GP can do blood tests for folate levels and homocysteine levels – if they are normal then even if you have the variant it isn’t affecting you adversely
Saliva tests are available online to check for the MTHFR variant. Prices start at £80.
summary - key points for helping fertility with folate
Preparation is key – start changing your diet and taking a preconception supplement before trying to conceive
Folic Acid as part of a prenatal will be adequate as a supplement for most women
Eating leafy green vegetables, berries and citrus fruit daily will supply Methylfolate
If you have had recurrent miscarriages or IVF failures consider switching to a prenatal containing L-Methylfolate
Don’t take folic acid on it’s own - choose a preconception or prenatal multivitamin with at least 2.5mcg B12
Men need folate for their fertility too
The technical bit
The terminology can get confusing…
MTHF is methylfolate (L-5-methyltetrahydrofolate) also known as L-methylfolate
MTHFR is the enzyme needed to produce methylfolate
MTHFR variant is the genetic variation
Homocysteine is an amino acid
how genetics affect the MTHFR enzyme
The enzyme needed to convert folic acid or folate into a usable form is called 5-MTHF reductase (MTHFR) – it allows recycling of the amino acid homocysteine to methionine.
If MTHFR levels are low then homocysteine levels can build up and this has been linked to infertility, miscarriage, birth defects, mental health problems and heart disease
High homocysteine causes oxidative stress and can affect DNA
Some people have a genetic variation called the MTHFR variant
There are about 30 types of variant
Each variant may be heterozygous or homozygous
A variant called C677T is the one that has been studied most
Homozygous C677T is linked to lower folate and higher homocysteine levels
Appoximately 10% of the UK population has the homozygous C677T variant and the incidence is higher in people of Mediterranean decent
