The Importance of Folate & Vitamin B12 When Trying to Get Pregnant

With the overwhelming amount of information on what to eat and which vitamins to take when trying to conceive, what is actually essential?  Are folate (vitamin B9) and vitamin B12 really that important?

Why are folate and vitamin B12 important when trying to get pregnant?  Both folate and B12 are active within the methylation cycle, which is foundational to many biological processes including DNA synthesis, repair, cell division - all critical for a health baby.

Should you be drinking kale and celery smoothies every morning? Organic lemons carefully squeezed into warm water?

We all know of women who eat fast food, potato chips – perhaps even (gasp!) cold pizza for breakfast – and yet still easily get pregnant!  Our grandmothers and great-grandmothers didn’t swallow handfuls of prenatal vitamins each morning before getting pregnant.

So how important is your diet in getting pregnant? Do you need prenatal vitamins that contain B12 and folate? Let’s take a look at some research to see what the scientific evidence says about vitamins and pregnancy.

What is vitamin B12?

Vitamin B12 is a water-soluble vitamin that is essential for your health. It is also known as cobalamin, which refers to its structure with a cobalt ion at the core.

Your body uses vitamin B12 in methylation cycle reactions. These methylation reactions turn on and off genes, convert serotonin to melatonin, change homocysteine to methionine, and more!

Vitamin B12 is also used in the mitochondria, those ‘powerhouses’ of the cell, converting fatty acids into energy.

Vitamin B12 deficiency:

Meats and dairy products are your dietary sources of B12, so deficiency can be a real problem if you are eating a vegetarian or vegan diet. Even if you are eating some animal product, medications such as heartburn remedies can disrupt your absorption of B12.

The symptoms of severe vitamin B12 deficiency include:

  • memory issues
  • mood swings
  • disorientation
  • numbness
  • appetite loss
  • constipation
  •  sore tongue

Vitamin B12 deficiency is also a cause of megaloblastic anemia. (study)

What is vitamin B9?

Folate, or vitamin B9, is a general term that refers to both naturally occurring folates in foods as well as synthetic folic acid.

Synthetic folic acid is often added to foods, such as flour, cornmeal, rice, and pasta. The structure of folic acid is a little different than naturally found folates. Folic acid is more chemically stable and cheaper so it can easily be added to processed foods and supplements.

Your body must convert either folic acid and natural folate into the active form called 5-methyltetrahydrofolate. The body uses folate in the methylation cycle as well.

The U.S. recommended daily allowance (RDA) for pregnancy is 600 mcg/day.  Foods high in folate include liver, dark, leafy green vegetables such as spinach, brussels sprouts, broccoli, mustard greens, asparagus.

Folate deficiency

Not getting enough folate in your diet can lead to a higher rate of neural tube defects as well as other birth defects. This prompted the U.S. government to mandate folic acid fortification in wheat and rice products in 1998. (study)

Folate and B12: together and in the right amounts

Both folate and B12 are active within the methylation cycle, which is foundational to so many biological processes.

Researchers have shown that both vitamins are essential in healthy pregnancies!

Over 62% of pregnant women are deficient in vitamin B12. The rates are even higher for vegans and long-term vegetarians. (study)

Studies on folate and B12 show:

A recent study investigated the role that folate plays in pregnancy. The study looked at women undergoing IVF, dividing the participants into three groups (low, medium, and high) based on folate levels. The women with high folate levels had more than double the likelihood of pregnancy. (study)

Another recent study noted that women referred for in-vitro fertilization were very likely to have inadequate B12 and folate levels. In fact, only 44% of the women had adequate  B12 levels and only 12% had optimal folate levels. (study)

When looking at embryo quality in IVF, researchers find that higher B12 correlates with better embryos. They also find that increased folate in follicles significantly increases the chance of pregnancy. (study)

This isn’t just important for moms-to-be: dads need vitamin B12 also!  A study showed that the amount of B12 in semen correlates to sperm concentration, which is important when trying to conceive. (study) Folate is also very important for sperm motility. Men who are taking acid-suppressing medications are at a higher risk for folate deficiency and infertility. (study)

Excess folic acid:

While having enough folate is vital for a healthy pregnancy, too much folic acid may be detrimental. Your body metabolizes, or breaks down, synthetic folic acid differently than folates from food sources. This can lead to unmetabolized folic acid in the bloodstream.

Researchers are still studying the impact of unmetabolized folic acid. Some studies have linked excess folic acid in mothers to an increased risk of autism spectrum disorder in their kids. Other studies, though, also point to the importance of having enough folate, with low folate also linked to an increased risk of autism. (study)(study)(study)

So if too much folic acid may cause problems, you may be wondering if the same is true of folate from foods such as leafy green veggies. This doesn’t seem to be the case!

Synthetic folic acid is a different chemical compound than folate found naturally in foods. It is metabolized in the liver rather than the intestines. Natural folates from foods are broken down in the intestines, so your body absorbs just the right amount. (study)(study)

The FDA has set the safe upper limit for folic acid at 1,000 mcg/day. If you are taking a prenatal supplement with 800 mcg plus eating fortified foods such as bread, cereal, pasta, or rice, you may exceed that limit.

Switching to a prenatal supplement with methylfolate helps you to avoid too much folic acid.

While excess unmetabolized folic acid may be a risk factor in pregnancy, one recent animal study showed that adding in vitamin B12 can reduce some of the effects. (study)

What about the foods you eat?

If you are having a hard time getting pregnant, take a good look at your diet. Yes, there are people who get pregnant while eating junk food and drinking soda, but -unsurprisingly – research shows that isn’t your best pre-conception diet.

A recent study investigated the diet of couples undergoing IVF treatment. The results showed that a Mediterranean style diet that was high in vegetables, fish, legumes, and olive oil increased the probability of pregnancy by 40%. Women eating the Mediterranean diet had higher RBC folate and vitamin B6 levels.  (study)

Another study, also on patients at an IVF clinic, found that those in the upper half of the ‘healthy’ diet pattern (fruits, nuts, vegetables, meat, dairy, olives, and legumes) were 86% more likely to become pregnant than those in the bottom of the ‘unhealthy’ pattern, which included junk food, mayo, and solid oils. (study)

How do your genes impact your diet?

So what is the perfect diet when trying to conceive?

We are all different – unique – and that perfect diet may be different for you that it is for someone else.

Your genes play a role in how your body breaks down and uses nutrients.  Some people may be fine with a diet of occasional fast food along with salads, but others need lots more folate-rich foods, such as green vegetables.

Genes involved in folic acid metabolism:

The MTHFR gene codes for the enzyme that is vital in the last step of converting folic acid into the active form used by the body. About 35-40% of the population carry a variant called MTHFR C677T. People with the variant have decreased enzyme function. Another MTHFR variant, A1298C, also reduces the enzyme function. Researchers find that the variant increases the risk of recurrent miscarriages. (study)(study)

Check your genetic data for rs1801133 (MTHFR C677T):

  • G/G: normal (wildtype)
  • A/G: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 40%
  • A/A: two copies of C677T (homozygous), MTHFR efficiency reduced by 70 – 80%

Check your genetic data for rs1801131 (MTHFR A1298C):

  • TT: normal (wildtype)
  • GT: one copy of A1298C allele (heterozygous), MTHFR efficiency slightly reduced
  • GG: two copies of A1298C (homozygous), MTHFR efficiency reduced

Your body must first convert synthetic acid into the active form used in the methylation cycle. The first step of that process uses an enzyme called dihydrofolate reductase (DHFR). There is a common genetic variant of this gene that decreases its function. Studies show that people taking higher amounts of folic acid (> 500mcg/day) who also carry the variant were more likely to end up with unmetabolized folic acid in their bloodstream. (study)

Check your genetic data for rs10991108:

  • Insertion/Insertion: better at metabolizing folic acid
  • Deletion/Insertion: reduced ability to metabolize folic acid
  • Deletion/Deletion: reduced ability to metabolize folic acid

Genes involved in vitamin B12:

There are actually four different types of vitamin B12 that you can get as supplements:

  • cyanocobalamin
  • methylcobalamin
  • adenosylcobalamin
  • hydroxocobalamin

The cyanocobalamin form is found in inexpensive supplements. It contains a cyanide molecule that is bound to the B12. While most people can detoxify the small amount of cyanide, the other three forms of vitamin B12 are the active forms more easily used by the body.

Understanding your COMT gene can help you determine the best type of vitamin B12 for your body. The COMT gene codes for an enzyme that breaks down the neurotransmitters, dopamine and norepinephrine.

COMT rs4680 changes the activity of the enzyme.

The G/G (or Val/Val) genotype has higher COMT enzyme activity, which leads to quicker clearance of dopamine and norepinephrine. People with this genotype usually do well with methylcobalamin.

The A/A (or Met/Met) genotype has lower COMT enzyme activity. People with this genotype sometimes find that taking both methylcobalamin and methylfolate together leads to mood swings with anxiety or irritability. The theory is that too many methyl groups flooding in leads to a rapid rise and fall of dopamine levels. People with the A/A genotype may find that adenosylcobalamin or hydroxocobalamin work well. (study)

Check your genetic data for rs4680:

  • G/G: higher COMT activity, methylcobalamin
  • A/G: intermediate COMT activity
  • A/A: 40% lower COMT activity, adenosylcobalamin or hydroxocobalamin

Getting enough folate and vitamin B12 is essential for a successful pregnancy. Knowing your genetics and working with a fertility expert can help you narrow down the best choices for your body.