If you’re trying to get pregnant in your late 30s or 40s, supplementing with folic acid is important to prevent birth defects in your future baby. However, most people are unaware that it's also essential for optimal fertility and improving your chances of conceiving.
How can folic acid increase fertility? Although associated primarily with the prevention of congenital malformations, adequate levels of folate is critical for healthy reproductive function such as improving egg quality, implantation, and reducing the risk of miscarriage.
Unfortunately, most women are taking the inferior form of this nutrient in their supplements. Find out how to increase your folate for optimal fertility and a healthy baby. Knowing your genetic risk for folate deficiency may also guide you as you’re trying to conceive.
Why is Folate Important for Fertility?
Vitamin B9 or folate is important in all aspects of pregnancy from pre-conception onwards.
Some of B9’s important functions are:
Regulating ovarian function, implantation, and embryo development.
Helping the body make healthy new cells with the production of DNA - important when cells are growing in size and number rapidly during egg maturation before ovulation, embryo development, and pregnancy establishment.
Preventing birth defects such as neural tube defects when baby’s brain and spinal cord doesn’t close properly, Trisomy 21, spina bifida, anencephaly, and others
Because of folate’s proven ability to reduce the incidence of neural tube defects by 62%, the U.S. requires fortification in certain foods, using the synthetic (and cheaper) version of B9, folic acid. (1)
In women, folic acid supplementation has been shown to improve fertility in a number of ways. It can…
decrease the risk of infertility due to ovulation issues by 59%. (2)
reduce the chance for miscarriage
In women undergoing IVF treatment, folic acid supplementation resulted in the following observations:
increased AMH levels
3.3 times higher chance of achieving pregnancy with IVF (3)
more eggs retrieved and higher estrogen levels during IVF
In men, semen quality improved after 90 days of folic acid supplementation, with improved sperm concentration, motility, and morphology. (4)
What is Folic Acid and Folate?
Folic acid and folate are often used interchangeably to refer to vitamin B9.
However, their chemical structures are different and should not be considered the same.
Folate occurs naturally in foods whereas folic acid is the synthetic form of vitamin B9.
B9 found in food (folate) is more available to your body for its many needs. The digestive system converts food folate into a usable form before entering the bloodstream.
The active form of B9 in your body is a folate known as 5-methyltetrahydrofolate (5-MTHF), L-methylfolate, 5-methylfolate, or, more simply, methylfolate.
“Folate” is derived from the Latin word “folium,” meaning leaf.
Because your body doesn’t store B9 in large amounts, you need a daily dose of it for optimal fertility.
Dark, leafy green vegetables such as spinach, brussels sprouts, broccoli, mustard greens, asparagus are excellent sources of folate. (5)
Surprisingly though, the best source of B9 is beef liver. Eating 2-3 servings per week when trying to get pregnant will increase your folate level very quickly.
Be Careful with Folic Acid
Folic acid is the man-made version of vitamin B9 and does not exist naturally in the human body.
It’s added to supplements like your prenatals and processed food products, such as flour, bread, pasta, rice, and cereals.
A concern of taking synthetic folic acid is that it may competitively interfere with bioactive folate, since folic acid binds more easily to receptors in your tissue.(5)
Unlike folate from food, the process of converting synthetic folic acid to the active form of vitamin B9 is slow and inefficient, requiring more steps.
Because the body does not convert synthetic folic acid into bioavailable methylfolate very well, little of the folic acid may actually be used.
In fact, one concern of high folic acid supplementation is that unused folic acid may build up in the blood with potential toxic effects.
MTHFR’s Importance for Fertility
MTHFR is a gene that codes for an enzyme (methylenetetrahydrofolate reductase) responsible for converting folate and folic acid to 5-MTHFR for your body to use in the methylation cycle.
The problem is that a large portion of the population carries a variant of MTHFR that decreases its ability to function optimally, thus impacting the methylation cycle.
This becomes more of an issue as a woman tries to get pregnant in her late 30s and 40s when poor egg quality is the primary reason for infertility.
What’s the big deal about the methylation cycle?
This is one of our body's essential biochemical processes that is necessary for a lot of functions including:
Detoxification of hormones including excess estrogen, chemicals, and heavy metals
DNA repair and production
Reduction of inflammation
Mitochondrial function and energy production to improve egg and sperm quality
Production of antioxidants to protect your cells, including the eggs and sperm
The methylation cycle works by transferring a methyl group to the molecule that needs it. A methyl group is simply three hydrogen atoms bound to a carbon atom (CH3). Simple, but vital to so many of our body's processes.
Our body's main way of getting methyl groups is from SAMe (s-adenosylmethionine), which donates a methyl group to other substances that need it. This methylation cycle process depends on SAMe getting that important methyl group from methylfolate, which is created using the MTHFR enzyme.
If you carry an MTHFR variant that causes a decreased ability to create methylfolate, this can become the sticking point in the methylation cycle. (6)
How do you know if you carry an MTHFR variant?
Because these genes are not routinely tested in women when trying to get pregnant, you can have a simple and easy genetic test through 23andMe.com or AncestryDNA.com to find out if you have a problem with your methylation cycle. It’s a simple, non-invasive test that’s mailed to you which you send back with your saliva sample for analysis.
Once your results are available, you can easily look at your raw DNA file to find out what variations you carry.
Check your data for rs1801133, MTHFR C677T variant
GG: normal (wildtype)
AG: one copy of C677T allele (heterozygous), MTHFR efficiency reduced by 35% (7)
AA: two copies of C677T (homozygous), MTHFR efficiency reduced by 80-90%,
Among Caucasians, around 10 % of people are AA and 40 % are AC. Only 50% have GG with normal MTHFR activity. In Asians, around 20% of people are AA. (8)
Check your data for rs1801131, MTHFR A1298C variant:
TT: normal (wildtype)
GT: one copy of A1298C allele (heterozygous), MTHFR efficiency slightly reduced
GG: two copies of A1298C (homozygous), MTHFR efficiency reduced
How does MTHFR relate to fertility?
Women who carry the MTHFR variants are at an increased risk for miscarriage. A meta-analysis of over 57 different studies found that both MTHFR C677T and A1298C were associated with an increased risk of miscarriage. (9)
For women with rs1801133, AA genotype, the risk of miscarriage was more than doubled.
For women with rs10801131, AA or AG genotype had an increased risk of miscarriage by 59%.
For women undergoing IVF,
rs1801133, AA genotype are at a more than double risk for recurrent implantation failure in IVF. (10)
rs1801133, AA genotype is associated with higher AMH concentrations and 20% fewer eggs retrieved with IVF compared to GG and AG (11)
rs1801133, AA or AG genotype had a higher risk of premature ovarian failure (POF) (12)
What should you do if you carry the variant?
While folate is important for everyone trying to conceive, it is especially important for women who carry the MTHFR variant.
Leafy green veggies and beef liver are both excellent dietary sources of folate. You know that it is important to get your greens in every day, but if you carry the MTHFR variant, it is truly essential when trying to conceive.
This isn't just a woman's issue.
Men who carry the MTHFR variant are more likely to have fertility issues, and male MTHFR variants are also linked to an increased risk of miscarriage. (13) (14) So get your partner on board with optimizing nutrition, joining you in eating more greens and beef liver.
What to Do if You have MTHFR ?
While the MTHFR variant is linked to an increased risk of miscarriage, that risk is reduced by getting enough folate to meet your body’s needs. This is one genetic variant that you can overcome with nutrition or supplements.
Note that I keep saying 'folate' and not folic acid. Too much folic acid is not helpful for women who carry the MTHFR C677T variant. In fact, some studies show that it may build up and be detrimental. (15)
Instead, opt for a prenatal vitamin that contains 800 mcg methylfolate or 5-MTHF, the active form of folate that avoids the MTHFR variant.
Can you take methylfolate as a supplement if you don't carry the MTHFR variant?
Absolutely and you should. You may not be getting enough folate from your food so supplementing is recommended. Dose is similar to folic acid, with 800 mcg recommended for women TTC.
In addition to getting enough folate, or supplementing with methylfolate, vitamin B12 is also important in the methylation cycle, so it is often advised to go with a B-complex that contains the active form of B12, methylcobalamin. Good food sources of vitamin B12 include liver, clams, beef, and nutritional yeast.
How long do I need to take folic acid before getting pregnant?
Because the baby’s neural tube closes by 28 days after conception, you need adequate levels BEFORE you get pregnant. Take folate as soon as you start trying to conceive. If however you get pregnant with less than 3 months of folate supplementation, you may need to supplement with a higher dosage in the first trimester.
My doctor recommends 5mg folic acid. Is that safe?
No. Such a high dose has risks that can be avoided by taking 800 micrograms of 5-MTHFR, the active form of folate that your body is able to use.
The conclusion of this June 2018 study states: “The conventional use of large doses of folic acid (5 mg/day) has become obsolete. Regular doses of folic acid (100-200 μg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound. A physiological dose of 5-MTHF (800 μg) bypasses the MTHFR block and is suggested to be an effective treatment for these couples. Moreover, it avoids potential adverse effects of the UMFA ((un-metabolized folic acid) syndrome, which is suspected of causing immune dysfunction and other adverse pathological effects such as cancer (especially colorectal and prostate).”
Broccoli “Cheese” Soup
Here’s an easy recipe for a generous dose of folate. Make a big batch for plenty of leftovers.
Prep Time: 10 minutes
Cook Time: 20 minutes
Total Time: 30 minutes
Ingredients: (Reminder - buy organic whenever possible)
2 tablespoons coconut oil
½ onion , diced
1-2 cloves garlic , minced
3 cups bone broth + more to thin out soup
4 cups broccoli florets
1 ½ cups shredded carrot , about 2 medium
1 cup raw cashews , soaked for 4 hours
½ teaspoon mustard powder or 1 tsp prepared mustard
½ teaspoon smoked paprika
½ cup nutritional yeast
1 tablespoon fresh lemon juice , about half a lemon
Cayenne pepper, dash
Freshly cracked pepper
Cooked pasture-raised bacon pieces (optional)
Avocado, diced (optional)
In a medium saucepan over medium heat, heat coconut oil. Add onion and sauté until translucent, stirring often. Add garlic and cook, stirring constantly, about 30 seconds, or until fragrant.
Add 2 cups bone broth, broccoli, and carrots. Cover with a lid. Simmer until broccoli is tender, about 6-8 minutes.
In a blender, combine cashews, water, mustard powder, smoked paprika, nutritional yeast, lemon juice, 1 cup bone broth, and cayenne pepper. Blend at high speed until very smooth.
Add broccoli mixture to blender and pulse a few times to incorporate, keeping small pieces of vegetables intact for texture.
Add sea salt and freshly cracked pepper to taste.
Thin out with bone broth to desired consistency. Spoon into serving bowls. Top with bacon and avocado.
Nutritional yeast provides the cheesy taste without actual cheese. However, if you’re prone to yeast infections, leave this out because it’s a deactivated yeast.
This recipe was derived from this post but I swapped out the liquids for bone broth to amp up the fertility factor.