Prenatal Vitamins: Folate vs. Folic Acid and the MTHFR Mutation
Why are prenatal vitamins so important?
“What should I take while trying to conceive?” This is a common question among people when they’re thinking about how to have the healthiest pregnancy possible. This is also an area with a lot of misconceptions and misinformation!
You may also be interested in 7 key nutrients your prenatal vitamins should include for more related to this topic.
Prenatal vitamins (PNV)
What is so special about prenatal vitamins? How are they different from a regular multivitamin?
And what exactly do they do for people trying to conceive (TTC)?
Prenatal vitamins are specially formulated multivitamins that cater to the increased nutritional needs of pregnant people. The Society of Obstetricians and Gynaecologists of Canada (SOGC) and the American College of Obstetricians and Gynecologists (ACOG) recommend prenatal vitamins because they contain higher levels of certain nutrients that are crucial during pregnancy, such as folic acid, iron, and calcium. They may also omit some vitamins or nutrients that may be harmful at high levels during pregnancy.
For example, a regular women’s multivitamin may contain 400 mcg of folic acid but the prenatal version may contain 1000 mcg of folic acid.
Folic acid (FA): Why does it matter?
Folic acid, a synthetic form of folate (a B vitamin), is vital for preventing neural tube defects (NTDs) in the developing fetus. NTDs can be severe birth defects of the brain and spine. Examples include conditions such as spina bifida, cleft lip, or cleft palate.
The SOGC and ACOG recommend that all women who can become pregnant or who are trying to conceive take a daily supplement containing at least 400 mcg of folic acid. They also recommend that a prenatal vitamin be started at least 3 months prior to conception, as folic acid is especially crucial during the first trimester of pregnancy as this is when the neural tube develops; read about prenatal screening and testing and prenatal vitamins and neural tube defects.
Who should take extra folic acid?
Women in intermediate- to high-risk categories for NTDs (such as women who have had an NTD-affected previous pregnancy, a family history of NTDs, insulin-dependent diabetes, or women who take certain epilepsy medications) should be advised that high-dose folic acid (1 mg to 4 mg daily) supplementation is recommended.
You should speak with your doctor to determine your personal risk and the appropriate level of folic acid supplementation: read the article.
Folate vs. folic acid and the MTHFR Mutation
While often used interchangeably, folate and folic acid differ slightly. Folate occurs naturally in foods, while folic acid is the synthetic form used in supplements and fortified foods.
Food or dietary folates are absorbed by the intestine, and through a sequence of chemical reactions, are converted to L-methyltetrahydrofolate or L-5-methylTHF, which is the active form of folate in the body. We’ll call this plasma folate for simplicity. The process of converting dietary folate to plasma folate happens in the intestine and the enzyme produced by the MTHFR gene is involved in the last step. Dietary folates are not that stable and are easily broken down by heat during cooking, so getting enough from an unfortified diet can be challenging.
Folic acid is a synthetic form of folate, meaning it is made in a lab. It is more easily absorbed than dietary folates, and, just like dietary folates, folic acid is converted to L-5-methylTHF or plasma folate in the bowel, and the last step involved also uses the enzyme MTHFR. Folic acid is also more easily absorbed from food than dietary folates and is not destroyed by heat. This is why it is used to supplement food.
Folic acid is the only form of folate that has been shown to reduce the risk of neural tube defects.
The MTHFR Mutation and its implications
The MTHFR gene produces the enzyme methylenetetrahydrofolate reductase, which converts 5,10-methylenetetrahydrofolate to the primary form of folate (L-5-methylTHF or plasma folate) that is used by the body. This gene is involved in many functions in our bodies.
There are two common or variations in the genetic code for the MTHFR gene, known as C677T and A1298C. These genetic variants are also known as “polymorphisms,” meaning they are common in the general population. In fact, 30-40% of people will have at least one copy of the C677T or A1298C polymorphism (variant), while some people may have a polymorphism on BOTH copies of the MTHFR gene.
There is also a synthetic version of L-5-methylTHF or plasma folate; we’ll call this synthetic 5-methylTHF. On the internet and on social media, it is being proposed as an alternative to folic acid supplementation. This is despite the fact that it has not been tested for this purpose and has not been shown to be effective.
We understand that it is certainly tempting to make the link between these pieces of information in an attempt to ensure the health of your baby.
As mentioned, there are some people with two copies of the variants in their MTHFR gene. Some people may then conclude that, if I am one of these people, then I should not take folic acid and I should take synthetic 5-methylTHF to make sure that I am getting the plasma folate levels I need to prevent neural tube defects.
The problem is that synthetic 5-methylTHF has NOT been studied in preventing neural tube defects. The current recommendation is not to order MTHFR testing or to use the results of MTHFR testing to describe the risk related to neural tube defects.
It is recommended that everyone attempting pregnancy take 400 mcg of folic acid as this is the ONLY intervention that has been shown to reduce neural tube defects!
Even people with two copies of the C677T polymorphism can process folic acid as well as those without these variations.
Folic acid supplementation is an important public health effort! One of the pivotal studies was published back in 1991 in the Lancet, a very prominent medical journal. This study was conducted at 33 centres in seven countries to determine whether supplementation with folic acid or a mixture of seven other vitamins (A,D,B1,B2,B6,C and nicotinamide) around the time of conception can prevent neural tube defects. A total of 1817 women at high risk of having a pregnancy with a neural tube defect, because of a previous affected pregnancy, were allocated at random to one of four groups- namely, folic acid, other vitamins, both, or neither. 1195 had a completed pregnancy; 27 of these had a known neural tube defect including 6 in the folic acid groups and 21 in the two other groups. This means that folic acid had a 72% protective effect!! The other vitamins showed no significant protective effect for NTDs. There was no known harm from the folic acid supplementation as well. See Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. (1991). Lancet (London, England), 338(8760), 131–137.
In 1998, the United States began mandatory fortification of wheat flour with folic acid; several other countries including Canada, South Africa, Australia, and countries in South America followed suit. In the United States, food fortification has been linked to a 19% decrease in all NTDs, with an 11% decrease in anencephaly and a 23% reduction in spina bifida (Honein MA, Paulozzi LJ, Mathews TJ, Erickson JD, Wong LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 2001;285:2981–6.). It has been estimated that between 16% and 58% of NTDs could be prevented by folic acid supplementation (Castillo-Lancellotti C, Tur JA, Uauy R. Impact of folic acid fortification of flour on neural tube defects: a systematic review [published erratum appears in Public Health Nutr. 2013;16:1527]. Public Health Nutr 2013;16: 901–11. (Systematic Review)) .
Who recommends folic acid for neural tube defect prevention?
- ACOG: The American College of Obstetricians and Gynecologists
- SMFM: The Society of Maternal-Fetal Medicine
- USPSTF: US Preventive Services Task Force
- ACMG: American College of Medical Genetics
- CDC: Centers for Disease Control and Prevention
- FDA: Food and Drug Administration.
- AAFP: American Academy of Family Physicians
- AAP: American Academy of Pediatrics
- AAN: American Academy of Neurology
- SOGC: The Society of Obstetricians and Gynaecologists of Canada
- RCOG: The Royal College of Obstetricians and Gynaecologists
- The Academy of Nutrition and Dietetics (FORMERLY the American Dietetics Association)
- The Food and Nutrition Board (FNB) of the National Academies of Sciences, Engineering, and Medicine, Health, and Medicine Division
The fortification of food with folic acid has been an important and impactful public health effort. All people with a uterus who are trying to become pregnant or who may become pregnant should be taking a prenatal vitamin with a minimum of 400mcg of folic acid every day. Even if you have a genetic change in your MTHFR gene, many, many expert groups still recommend folic acid supplementation at the same dose because there is a mountain of evidence showing that this significantly decreases the rate of MTDs and makes for healthier babies!
Read more about Everything you need to know about prenatal vitamins and other supplements in pregnancy and when TTC
Folate vs. Folic Acid: What’s the Difference?
Include a comparison table.
| Feature | Folate | Folic Acid |
|---|---|---|
| Source | Naturally found in foods | Synthetic form used in supplements and fortified foods |
| Examples | Spinach, lentils, asparagus, avocado | Prenatal vitamins, fortified cereals |
| Bioavailability | Naturally occurring | Highly stable and well absorbed |
| Activation | Already in natural food form | Must be converted by the body into active folate |
| Primary Use | Daily nutrition | Prevention of neural tube defects and supplementation |
| Suitable During Pregnancy | Yes | Yes, unless otherwise advised by your healthcare provider |
What Is the MTHFR Gene?
Explain:
- What the MTHFR gene does
- Its role in folate metabolism
- Common genetic variants (C677T and A1298C)
- How mutations may reduce enzyme activity
- Why having an MTHFR mutation does not automatically mean infertility or pregnancy complications
Keep this section balanced and evidence-based.
Does an MTHFR Mutation Affect Fertility or Pregnancy?
Discuss:
Female Fertility
- Current evidence
- Miscarriage research
- IVF outcomes
Pregnancy
- Neural tube defects
- Importance of adequate folate intake
- Medical monitoring when appropriate
Male Fertility
- Limited evidence
- Ongoing research
Folate-Rich Foods
Include a table.
| Food | Good Source of Folate |
|---|---|
| Spinach | ✓ |
| Kale | ✓ |
| Lentils | ✓ |
| Chickpeas | ✓ |
| Broccoli | ✓ |
| Asparagus | ✓ |
| Avocado | ✓ |
| Oranges | ✓ |
Mention that diet alone may not provide sufficient folate during pregnancy.
Choosing the Right Prenatal Vitamin
Cover:
Standard Prenatal Vitamins
- Usually contain folic acid
- Recommended before conception
- Recommended throughout early pregnancy
Methylated Folate Prenatal Vitamins
Explain:
- 5-MTHF
- When a physician may recommend it
- Why patients should avoid switching supplements without medical advice
Include a note that most major obstetric guidelines continue to recommend adequate folic acid intake to reduce the risk of neural tube defects.
Should You Get Tested for an MTHFR Mutation?
Discuss:
- When testing may be appropriate
- Situations where routine screening is not generally recommended
- Importance of discussing testing with a fertility specialist or obstetrician
When to Speak With a Fertility Specialist
Include:
- Recurrent miscarriage
- Difficulty conceiving
- Previous pregnancy affected by a neural tube defect
- Family history
- Questions about prenatal supplementation
Conclusion
Summarize that both folate and folic acid play important roles in pregnancy and fertility. While MTHFR mutations have received significant attention, most individuals can achieve healthy pregnancies with appropriate prenatal care and evidence-based supplementation. Encourage readers to consult their healthcare provider before making changes to prenatal vitamins.
FAQs
What is the difference between folate and folic acid?
Folate is the naturally occurring form of vitamin B9 found in foods such as leafy green vegetables, legumes, and citrus fruits. Folic acid is the synthetic form used in fortified foods and many supplements. Both help support healthy cell growth and fetal development.
Should I take methylated folate instead of folic acid if I have an MTHFR mutation?
Some healthcare providers may recommend methylated folate (5-MTHF) for individuals with certain MTHFR variants. However, many people with MTHFR mutations can still use folic acid effectively. Speak with your healthcare provider before changing supplements.
Can an MTHFR mutation cause infertility?
Current research has not established that MTHFR mutations alone directly cause infertility. Fertility is influenced by many genetic, hormonal, anatomical, and lifestyle factors.
Do prenatal vitamins contain folic acid?
Yes. Most prenatal vitamins contain folic acid because it has been shown to reduce the risk of neural tube defects when taken before conception and during early pregnancy. Some formulations contain methylated folate instead.
Should everyone be tested for an MTHFR mutation before pregnancy?
Routine MTHFR testing is generally not recommended for everyone planning a pregnancy. Your healthcare provider may recommend testing in specific clinical situations based on your medical or family history.
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