Folate, folic acid, and which dosage???

Is it only me, or does it really get a bit confusing, that whole fuss about what exactly to supplement during preconception: folic acid and/or folate and which dosage?

Folic acid reduces the risk of severe neural tube defects

First of all, there is no doubt that if you’re pregnant or might become pregnant, it’s critically important to get enough folic acid.
This B-vitamin helps to decrease the risk of neural tube defects (NTDs), which are serious birth defects of the spinal cord (such as spina bifida) and the brain (such as anencephaly). The neural tube is the part of the embryo from which a baby’s spine and brain develop. In the US, NTDs affect about 3,000 pregnancies a year.
Health authorities of most countries recommend that women supplement at least 400 µg folic acid from at least one month before conception and during the first trimester of pregnancy to reduce their baby’s risk of neural tube defects by up to 70 percent. Some research suggests that folic acid may also help lower a baby’s risk of other defects, such as cleft lip, cleft palate, and certain types of heart defects.
Supplementation well before conception is critically important, as neural tube defects occur at a very early stage of development, before many women even know they’re pregnant.
However, there seems to be some confusion with respect to which form of folic acid to use for supplementation, with some people claiming so-called folate to be superior to folic acid. Now what exactly is the difference between the two?

Folate versus folic acid

Folate is the generic term for both naturally occurring food folate and folic acid, the synthetic form of the vitamin that is used in dietary supplements and fortified foods. The bioavailability of food folate is much lower than that of synthetic folic acid, commonly estimated at 50% of folic acid bioavailability. In addition to that, folic acid is much more stable than food folates. This is why folic acid is usually preferred for supplementation.

Folic acid metabolism

Importantly, the body needs to convert both food folate as well as synthetic folate to the active form prior to actually being able to benefit from its presence. The active form is 5-methyltetrahydrofolate (5-MTHF). In the digestive system, the majority of dietary folate is converted into 5-MTHF before entering the bloodstream. Unlike most folate, the majority of folic acid is not converted to the active form of vitamin B9, 5-MTHF, in the digestive system. Instead, it needs to be converted in the liver or other tissues. The conversion is catalyzed by an enzyme called MTHFR (methyl tetra hydro folate reductase) and effectiveness of folate / folic acid conversion in the body depends on its presence and function. 8 – 10 % of people are thought to have a genetic variant of the enzyme, rendering it less effective. These persons may wonder whether the usually recommended supplementation of 400 µg folic acid from preconception is enough.

Active folate or folic acid?

Basically there are two ways to make sure these people get the required amount nevertheless: either they opt for taking 400 µg of the active form of folate, or they double the recommended dosage to 800 µg of folic acid daily in order to achieve the protective folate level in blood.

The American Center for Disease Control (CDC) clearly recommends to prefer folic acid over the active form of folate, because there is so much scientific data available on folic acid use, while there are only few studies that have been done with active folate:

” Folic acid is the only type of folate shown to help prevent neural tube defects.”

According to Professor Christian Thaler (Head of the Department of Endocrinology and Assisted Reproduction of the University of Munich / Germany), this dosage also benefits fertility and improves treatment outcomes in IVF patients with the genetic variant.
Taking this higher level of folic acid is also an interesting option for those of you, who don’t want to wait for pregnancy too long: it has been shown that you can achieve the protective folate blood level much faster with this dosage.
Data published by Jorge Chavarro, Associate Professor of Nutrition and Epidemiology at the Harvard School of Public Health, showed that this higher dosage is also preferable with respect to other aspects: after assessing huge amounts of data from the American Nurses’ Health Studies I and II, he concluded that an intake of more than 730 µg of folic acid daily was associated with reduced risk of spontaneous abortion and stillbirth.

Based on this data, every woman planning for pregnancy can feel on the safe side by supplementing 800 µg folic acid daily from at least one months prior to conception and throughout the first trimester of pregnancy (e.g. by taking Fertilovit®F35plus, or its equivalents for women with thyroid autoimmunity, endometriosis or PCOS).

References

https://www.cdc.gov/ncbddd/folicacid/mthfr-gene-and-folic-acid.html

Chavarro JE, Rich-Edwards JW, Gaskins AJ, Farland LV, Terry KL, ScD, Zhang C,
Missmer SA, Contributions of the Nurses’ Health Studies to Reproductive Health Research AJPH 2016, Vol 106, No. 9

Pietrzik K. et al.: Randomized, placebo-controlled, double-blind study evaluating the effectiveness of a folic acid containing multivitamin supplement in increasing erythrocyte folate levels in young women of child-bearing age. Ann of Nutr & Metab 2005; 6.7.29: 368

Thaler CJ. Folate Metabolism and Human Reproduction. Geburtshilfe Frauenheilkd. 2014 Sep;74(9):845-851.