Folic Acid for Fertility

Folic acid is the synthetic form of folate (vitamin B9). Multiple studies have concluded that daily folic acid supplementation in the periconceptional period can both prevent neural tube defects (NTD) and possibly also improve reproductive success in women.

Research suggests that folic acid from fortified foods and supplements is associated with:¹

• lower risk of ovulatory infertility (irregularity or failure of the ovaries to release an egg during a menstrual cycle)
• faster conception
• greater success with infertility treatment

Folic acid is thought to support fertility by improving menstrual cycle function. Studies suggest that taking folic acid can help to balance reproductive hormones and enhance follicular development.

Folate is essential for methylation and normal DNA/RNA synthesis and repair. Low folate levels lead to reduced cell division, increased production of inflammatory cytokines, higher oxidative stress, and apoptosis (cell death).² These effects can all lead to degeneration and resorption of ovarian follicles that fail to ovulate (follicular atresia) and reduced ovarian reserve.

Folate is also critical for the metabolism of homocysteine, and low folate levels can lead to elevated levels. High homocysteine (hyperhomocysteinemia) is shown to impair follicular growth, oocyte competence, embryo quality, and endometrial receptivity, increasing the risk of implantation failure, miscarriage, and pregnancy complications.³

Studies in women undergoing infertility treatment also suggest that folic acid intake could improve fertility by supporting oocyte and embryo quality.

Several studies have shown that folic acid intake appears to improve ovulation. 

A 2023 study examining dietary folate intake and antral follicle count (AFC) among women being treated for infertility found that higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve. The study referred to folate from supplements and fortified foods, which is typically folic acid.⁴

Folate deficiency can lead to elevated homocysteine, which is associated with increased inflammation⁵, reduced nitric oxide bioavailability, oxidative stress, apoptosis, and impaired methylation.⁶ These effects can then result in follicular degeneration. Previous studies show that women taking folic acid have lower homocysteine and higher quality oocytes.⁷

While some sources have suggested that the increased rates of twinning in the 90s were linked to increased intake of folic acid, there is no scientific evidence that folic acid actually increases the chance of twins.⁸

A 2016 Danish study suggested that folic acid supplementation increased the chances of conception within a single menstrual cycle, resulting in a shorter time to pregnancy. This was especially apparent in women with irregular cycles, and women with either short or long cycle length.⁹

Low folate levels can lead to higher homocysteine, which then reduces the chances of getting pregnant.¹⁰ Increasing folate levels by taking folic acid (or other forms of folate) can reduce homocysteine, which may then improve fecundity.

In the US, women planning pregnancy are advised to take 400 micrograms of folic acid daily, starting at least 1 month before conception.¹¹

• Methylfolate
  Methylfolate is the active, bioavailable form of folate. Unlike folic acid, it does not require conversion in the body before it can be used, which is beneficial for those with genetic variants such as MTHFR who lack the enzyme required for this conversion process. Research has shown that taking a methylfolate supplement alongside B6 and B12 can lower homocysteine levels more effectively than high-dose folic acid. This is because methylfolate, B6 and B12 directly contribute to the remethylation of homocysteine.¹² Recent research has suggested that methylfolate supplementation during pregnancy is preferred over folic acid for its ability to bypass the block in folic acid metabolism linked to enzymatic impairments. Methylfolate also avoids the risk of Unmetabolized Folic Acid (UMFA) syndrome, which has been linked to high-dose folic acid intake.¹³
  
  
• Dietary folate
  Folate is naturally present in foods such as green leafy vegetables, legumes, eggs, and citrus. However, food alone should not be the sole source of folate during pregnancy due to the high bodily requirements. The bioavailability of natural folate from food is only around 50%.¹⁴ This can be reduced further by poor digestive function, low nutritional content of the food itself, genetic profiles, and so on.
  
  
• Folic acid
  Folic acid supplementation was introduced after a 1991 study found that it could prevent neural tube defects (such as spina bifida and anencephaly) caused by folate deficiency. The trial showed 83% protection against neural tube defects in women taking 400 µg folic acid daily before conception. However, researchers noted that 17% were not helped by folic acid, possibly due to genetic factors.¹⁵
  Folic acid is a cheap source of folate and is often used in prenatal supplements. It is also added to many fortified foods such as cereals, breads, and juices. However, people with certain genetic variants, such as MTHFR, are unable to properly metabolize folic acid, which can lead to both folate deficiency and unmetabolized folic acid syndrome (UMFA).
  UMFA occurs when intake exceeds the body's ability to convert it properly - usually at doses over 200 mcg. Over 95% of Americans have detectable UMFA in their blood, with levels especially high in older people and supplement users.¹⁶ High UMFA levels are associated with decreased natural killer (NK) cell activity, which affects immune system function, and impaired methylation, which affects neurotransmitter production and DNA repair.¹⁷
  UMFA can also mask vitamin B12 deficiency, which can have a serious impact on pregnancy. Animal studies show that high-dose folic acid supplementation can increase rates of genetic mutation 1.8-fold by hypermethylating DNA repair genes and impairing DNA repair activity.¹⁸

Conception depends on many different factors: your physical and mental health, health history, diet, lifestyle, genetic background, environment, and more. While no supplement or treatment can ‘guarantee’ conception, there are several steps you can take to optimize your chances.

A general check-up with your doctor should involve an overall health assessment, including routine blood tests for iron, vitamin D, folate, and B12. Cervical screening should also be considered, as well as whether your vaccinations are up to date. 

If you have a family history of genetic health conditions, it may be a good time to have a genetic screening test. Hereditary conditions such as cystic fibrosis, spinal muscular atrophy (SMA), sickle cell anemia, or other genetic variants can help assess the risk of passing conditions to a child.

Your own physical and mental health history should also be considered, particularly if you are affected by cardiovascular issues, genetic variants, nutritional deficiencies, or other concerns.

Eating a balanced diet and exercising regularly is essential for the health of both the mother and infant during pregnancy. A healthy body weight can also improve your chances of conception. If you have dietary restrictions or nutritional deficiencies, it may be a good idea to see a dietician or nutritionist for a personalized plan.