Folate and Folic Acid in Pregnancy

Folate and its cousin folic acid are vital for developing a healthy baby because it prevents neural tube defects. Since the neural tube develops within the first 28 days of pregnancy, it is recommended all women of childbearing years consume folate. Folate prevents certain heart abnormalities, cleft palate and cleft lip. It also lowers the risk of developing anemia, miscarriage, preterm delivery and low birth weight. It can be found in fortified breakfast cereals, lentils, spaghetti, rice, beans, broccoli, orange juice, spinach and strawberries.

What is the Role of Folate and Folic Acid in Pregnancy?

Folate (vitamin B-9) is important in red blood cell formation and for healthy cell growth and function. The nutrient is crucial during early pregnancy to reduce the risk of birth defects of the brain and spine. The recommended daily amount of folate for adults is 400 micrograms (mcg). Women who are planning pregnancy or could become pregnant are advised to consume 400 to 1,000 mcg of folic acid a day.

Folate is found mainly in dark green leafy vegetables, beans, peas and nuts. Fruits rich in folate include oranges, lemons, bananas, melons and strawberries. The synthetic form of folate is folic acid. It’s in an essential component of prenatal vitamins and is in many fortified foods such as cereals and pastas.

A diet lacking foods rich in folate or folic acid can lead to a folate deficiency. Folate deficiency can also occur in people who have conditions, such as celiac disease, that prevent the small intestine from absorbing nutrients from foods (malabsorption syndromes).

What’s the difference between Folic Acid and Folate?

People often use the two interchangeably as they are both forms of vitamin B9 but in fact there is an important difference. Folic acid is the synthesized version that is commonly used in processed foods and supplements. Folate can be found in whole foods such as leafy vegetables, eggs, and citrus fruits.
Research on use of folate and oral folic acid supplements for specific conditions shows:
  • Birth defects. Research has shown that folic acid supplements can prevent birth defects of the neural tube. Taking a daily prenatal vitamin — ideally starting three months before conception — can help ensure women get enough of this essential nutrient.
  • Folic acid deficiency. Nutritional folate deficiency is treated with oral folic acid supplements. This type of deficiency is no longer a problem in many countries that fortify foods such as cereal and pasta with folic acid.
  • Heart and blood vessel disease and stroke. Folic acid works with vitamins B-6 and B-12 to control high levels of homocysteine in the blood. Elevated homocysteine levels might increase your risk of diseases of the heart and blood vessels (cardiovascular disease).
  • Cancer. Some research suggests that folate might reduce the risk of various cancers.
  • Depression. Some evidence suggests that folic acid might be helpful in treating depression.
  • Dementia. There isn’t enough evidence to support folic acid supplementation for the prevention of dementia.

Dr. Chris D. Meletis explains how genetics can determine how well your body metabolizes Vitamin B9

It is estimated that between 25 and 60 percent of the population have a variation in one of their MTHFR genes that negatively impacts their ability to convert folic acid (the synthetic version of B9), and even some of the folate that naturally occurs in foods, into the active form of folate.  If you are trying to get pregnant, consider getting your genes tested to determine if you have the MTHFR genetic variation. Knowledge will give you the power to make informed choices about your unique nutritional needs, including whether or not you should choose prenatal and fertility supplements that contain the active, methylfolate form of folic acid.

MTHFR Converts Synthetic to Bioactive Vitamin B9

Vitamin B9 is found as either the synthetic form (folic acid) that appears in many vitamin supplements and fortified foods or the naturally occurring form found in foods (folate). Both the synthetic and most of the food-derived folate we consume must be converted via a natural enzyme pathway in our body to the final bioactive form called L-methylfolate (also known as 5-MTHF). Once MTHF is created, this active form of B9 can enter cells and cross over the blood brain barrier to help nourish our tissues and brains. Successful conversion from folic acid or folate to MTHF is dependent upon a converting enzyme known as MTHFR.

MTHFR is the cause of elevated homocysteine levels tied to frequent miscarriages

Homocysteine is a naturally occurring amino acid produced when proteins are broken down in the body. It is not harmful at low levels, but when present in high concentrations it can lead to a condition called hypercoagulability, in which your blood tends to clot more easily than it should.  Women with elevated homocysteine levels are believed to be at higher risk for miscarriage, preeclampsia and even preterm labor – most likely due to the increased clotting caused by the elevated homocysteine levels.

Why do homocysteine levels become elevated? Methylfolate, the active form of folic acid, plays a role in converting homocysteine into methionine (a harmless amino acid), so if methylfolate is lacking due to the MTHFR mutation and subsequent inability to convert folic acid to methylfolate, homocysteine can build up to dangerous levels.

Researchers have discovered an association between high homocysteine levels and recurrent miscarriage, which suggests that the MTHFR genetic variation may play a role in pregnancy loss.

The  link between MTHFR and PCOS

The most common specific condition that causes infertility in women is polycystic ovary syndrome (PCOS).  Women with PCOS are prone to hormonal and metabolic imbalances, including blood sugar dysregulation, also known as insulin resistance. These metabolic issues can cause chronic anovulation (when ovaries do not release an oocyte during a menstrual cycle), oligomenorrhea (irregular periods), hyperandrogenism (too much testosterone) and insulin-resistance. Given this wide range of fertility-related symptoms, it is not surprising that PCOS is a leading cause of infertility.

Many studies are being done to understand the underlying causes of PCOS. A 2014 study found a connection between PCOS and MTHFR gene mutations, with the researchers concluding that a specific MTHFR mutation increases susceptibility to PCOS. The common thread between MTHFR and PCOS once again has to do with homocysteine levels. In general, the most common cause of elevated homocysteine levels (hyperhomocysteinemia) is reduced activity of MTHFR, which results in reduced production of methylfolate. Women with PCOS typically test positive for higher homocysteine levels than other healthier women. Many more studies are currently underway to determine the exact relationship between MTHFR and PCOS.

Active Folate vs Folic Acid

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References

  • Folate (folic Acid) Mayo Clinic
  • Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients. Gynecol Endocrinol. 2017 Dec 21:1-7.
  • Maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of recurrent pregnancy loss. J Dev Orig Health Dis. 2012 Oct;3(5):327-32.
  • Association of methylenetetrahydrofolate reductase gene C677T polymorphism with polycystic ovary syndrome risk: a systematic review and meta-analysis update. Eur J Obstet Gynecol Reprod Biol. 2014 Jan;172:56-61.
  • MTHFR C6777T polymorphism is associated with hyperlipidemia in women with polycystic ovary syndrome. J Hum Reprod Sci. 2012 Jan-Apr; 591):52-56.
  • Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: evidence from 25 case-control studies. PLoS One 2012:7(10):e41689.