
Snapshot
Folate, also known as folic acid in its synthetic form, is a crucial vitamin not only for pregnancy but also for conception itself. New research suggests that taking folate can enhance egg quality, restore ovulation, and reduce the risk of miscarriage.
◊What is folate?
Folate is a type of B vitamin (B9) that plays a crucial role in many biological processes within the body. It supports healthy cell division and is essential for proper foetal growth and development. Folic acid, the synthetic form of folate, is commonly found in pregnancy supplements and fortified foods.
◊The importance of folate for fertility?
Folate is well-known for its role in preventing serious birth defects, such as spina bifida. Newer research also suggests that folate plays a key role in egg development, which begins 3-4 months before ovulation. This means that starting folate supplementation early (at least months prior to conception) is beneficial for those trying to fall pregnanc.
Recent studies highlight the importance of folate at every stage of fertility, from egg development to ovulation to supporting healthy foetal growth (1).
•Folate and Ovulation
For years, doctors have suspected that vitamin deficiencies contribute to ovulation problems. Studies show that women who take a daily multivitamin are significantly less likely to experience infertility related to ovulation. In fact, several studies have found higher pregnancy rates in women who took a daily multivitamin than those who took a placebo (2).
In addition, a diet rich in folate has been shown to increase progesterone levels, reducing the risk of ovulation disorders (2). You can find a list of foods high in folate later in this article.
•Folate and Egg Quality
Folate also appears to improve egg quality and increase IVF success rates. Women who take folic acid supplements before IVF cycles have been found to have higher quality eggs and a greater proportion of mature eggs compared to those who do not take additional folate. In one study, researchers found that women with twice the usual levels of folate in their ovarian follicles were three times more likely to become pregnant.
◊Methylfolate vs. Synthetic Folic Acid
Methylfolate and folic acid are both forms of vitamin B9, but they differ in their absorption and utilisation in the body:
- Methylfolate is the active, natural form of folate that your body can use directly. It is involved in crucial processes such as DNA synthesis, repair, and detoxification. Methylfolate is readily absorbed and utilized, making it particularly beneficial for those with certain genetic variations, such as the MTHFR gene mutation, which affect folate metabolism.
- Folic Acid is the synthetic form of vitamin B9 found in supplements and fortified foods. It must be converted into methylfolate in the body before it can be used. This conversion process involves several steps and is less efficient in some individuals, particularly those with genetic variations that impair this conversion. High levels of unmetabolised folic acid can accumulate in the bloodstream, potentially interfering with the absorption of methylfolate.
In summary, while both forms provide folate, methylfolate is the biologically active form that is directly utilized by the body, whereas folic acid needs to be converted into methylfolate before it can be used.
◊MTHFR Gene Mutation
If you have a history of infertility or recurrent miscarriage, you may have a genetic mutation that affects your ability to metabolise folate. A 2016 study found that women with certain variants of the MTHFR gene, which is involved in folate metabolism, were more likely to have chromosomally abnormal embryos, experience implantation failure, and have lower chances of pregnancy through IVF (3). The MTHFR gene encodes an enzyme that converts folate into its active form, methylfolate, which plays a key role in detoxification. Our body’s use methylfolate to remove unwanted byproducts like homocysteine, a compound that can accumulate if folate metabolism is impaired.
Certain common variations in the MTHFR gene reduce the enzyme’s ability to produce methylfolate from other form of folate, such as folic acid. The resulting lower level of available methylfolate reduces its detoxification functions, leading to higher homocysteine levels. These higher homocysteine levels are thought to contribute to infertility and possibly miscarriage in people with the MTHFR gene mutation (4).
The two most common variants of the MTHFR gene are A1298C and C677T. About 40% of people carry one copy of the A1298C variant, which leads to a 20-40% reduction in enzyme activity. Having two copies of A1298C, or one or two copies of the C677T variant, can reduce enzyme activity by up to 70%. This more significant reduction affects around 10% of the population and is linked to higher homocysteine levels. However, the association between these gene mutations and recurrent miscarriage remains contentious.
◊Do I Need to Be Tested for the MTHFR Gene?
The good news is that the risks associated with MTHFR mutations can be mitigated with the right supplements. While you can ask your healthcare provider to order a blood test to determine your MTHFR genotype, it’s not necessary. You can simply opt for a prenatal vitamin that contains methylfolate or folinic acid, which are more easily metabolized forms of folate, regardless of your genetic status.
◊How do I know which folate to take?
Even if you don’t have a mutation in the MTHFR gene, it’s still beneficial to choose a prenatal supplement that contains methylfolate or another natural form of folate, rather than synthetic folic acid. Processing synthetic folic acid is inefficient and varies significantly between individuals, even without MTHFR variants. Studies have shown that a substantial amount of synthetic folic acid can remain unmetabolized and unusable. In some cases, this unmetabolized folic acid may accumulate, interfering with the uptake of methylfolate.
Other natural forms of folate, such as folinic acid (calcium folinate), are quickly converted into methylfolate. Therefore, it’s best to choose a prenatal vitamin with natural folates like methylfolate or folinic acid, whether or not you have a known MTHFR variant (3).
◊What dose of folate do I need daily?
Your total folate should be at least 500 micrograms daily (4).
◊ Can I get folate from food?
Yes, folate can be absorbed from a variety of foods. Some excellent sources include:
- Vegetables: particularly leafy greens, broccoli, brussel sprouts, cabbage, kale, spinach, peas, asparagus, beetroot, edemane beans, lettuce, avocadoes
- Legumes: chickpeas, kidney beans, lentils
- Peanuts
- Sunflower seeds
- Wholegrains
- Eggs
- Citrus fruits
- Beef liver (contraindicated in pregnancy).
Including these foods in your diet can help meet your folate needs and support overall health.
◊Do men need folate too?
Folate plays an important role in male fertility, particularly in supporting healthy sperm production and quality. Research suggests that adequate folate levels can help reduce the risk of chromosomal abnormalities in sperm, potentially lowering the chances of birth defects. Additionally, men with higher folate intake have been shown to have better sperm count, motility, and morphology, all of which are key factors in fertility. Folate’s role in DNA synthesis and repair is believed to contribute to these improvements.
◊Is folate still important when I‘m not trying to get pregnant?
Yes, folate is essential for overall health due to its role in key bodily processes like DNA synthesis, cell division, and the production of red blood cells. It supports brain function, heart health, and immune function by helping regulate homocysteine levels, which, when elevated, are linked to cardiovascular diseases. Folate also promotes healthy skin, hair, and nails, and may reduce the risk of certain cancers by aiding in DNA repair. Ensuring adequate folate intake helps maintain optimal health, even when pregnancy is no longer the goal.
◊References
- Chavarro, Jorge E. et al. Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility. Fertility and Sterility, Volume 89, Issue 3, March 2008. Link to article
- Gaskins, A. J. et al. Association between serum folate and vitamin B-12 and outcomes of assisted reproductive technologies. The American Journal of Clinical Nutrition, Vol 102, Issue 4, Oct 2015. Link to article
- Enciso M, Sarasa J, Xanthopoulou L, Bristow S, Bowles M, Fragouli E, Delhanty J, Wells D. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet. 2016 May;135(5):555-568. Link to article
- Kos, B. J. P., Leemaqz, S. Y., McCormack, C. D., Andraweera, P. H., Furness, D. L., Roberts, C. T., & Dekker, G. A. (2018). The association of parental methylenetetrahydrofolate reductase polymorphisms (MTHFR 677C > T and 1298A > C) and fetal loss: a case–control study in South Australia. The Journal of Maternal-Fetal & Neonatal Medicine, 33(5), 752–757. Link to article
- RANZCOG Guidelies Link to guidelines