Photo by Edgar Castrejon on Unsplash

June 4, 2018

This weeks article is written in collaboration with Dr. Mike Stadler. He is an Obstetrician with a passion for his patients and a preventative bend to his care. Like his partner, Dr. Grey, he is always looking for ways to enhance health with small actionable changes.

Since the early 1990's, the American medical community has recommended prenatal vitamins with folic acid as a supplement for mother's to be prior to and during the first 3 months of pregnancy. The thought was that this synthetic vitamin would be specifically targeting a group of congenital disorders called neural tube defects. These disorders are problems where the spinal cord does not form correctly and causes much childhood morbidity. Later on in the 90's, the government went a little further by adding folic acid to shelf stable foods like breads and cereals with the goal of increasing young women's exposure to the synthetic micronutrient. .

The initial effect of this program was a significant reduction in neural tube defects from 25% to 50% in different studies in different countries.

This was a resounding success from a public health perspective. However, as with how cholesterol reduction has not answered the question of coronary artery disease, folic acid supplementation has not completely resolved the problem.

What are we missing? Where is the piece that completes the puzzle?

It is clear from the literature that the neural tube and many other embryological pathways are established and completed very early in pregnancy. Therefore, it is critical that we provide a mother to be with all of the necessary macro- and micro-nutrients to allow for these embryological pathways to proceed as nature intended them to.

As we performed a deep dive into the literature, it became very clear that the pathways involved in neural tube development are complicated and well beyond just vitamin B9 or folate. The neural tube closes before the first month of pregnancy is complete, well before most mothers are aware of the pregnancy. Thus, it is critical to prepare for pregnancy and not be reactionary. It appears that adequate and functional levels of vitamin B12, choline and betaine are also necessary for pathways to process and proceed with normal fetal development. Let us look at some specifics.

There are cassettes of genes that when altered over time are putting mothers and their offspring at increased risk. These genes have SNP's, single nucleotide polymorphisms, that make the metabolism of folate, B12 and choline less functional. This puts extra pressure on the mother to increase her intake to meet the needs of her body based on her gene makeup. For example, a gene called MTHFR, methyl tetrahydrofolate reductase, is involved in folate metabolism. If it has a SNP that changes its function, then a mother would need significantly more folate to effect the same change in pathway development. This means that she is at higher risk for a child with a neural tube defect or other poor offspring outcome if she does not consume enough folate. The genes MTRR, MTR, MTHFD1, DHFR, CHKA, CUBN, and others are candidates for further study in this realm.

This is the critical part of the story. Most of us have no clue what our folate, B12, choline metabolic pathway genes are and cannot make an educated decision without this knowledge. Therefore, we must make best guess decisions for the population as a whole based on the unknowns.

Going back to the early 1990's, scientists had a good idea to fortify foods and also add folic acid to prenatal vitamins based on the available science. However, as with many things in life, we don't know in advance what the unintended consequences of a decision are.

Over the past half-decade, there continues to be a stream of evidence that folic acid may not be the best choice to supplement prenatally. Folic acid is synthetic and appears to bind the folate receptor preferentially over natural folate. It also must be metabolized in the liver to the active form unlike food-based folate. If a mother and or her offspring have SNP's related to folate metabolism, then there is evidence that the folic acid may not be metabolized correctly and that the unmetabolized form of folic acid circulates around the body. This does not appear to be good.

In a recent study by Emily McGowan from the University of Virginia presented at the AAAAI conference this year, her group noted that there was a strong association between food allergy and the higher quartiles of unmetabolized folic acid and lower levels of natural folate in the baby's blood at birth but not later in life pointing to a embryological effect. In another study by Dr. Wiens and colleagues in the Journal Brain Sciences, they looked at the risk of Autism in relation to unmetabolized folic acid levels. They have a nice review of the mechanisms and the current data as of November 2017.

We will say this, it is not settled whether synthetic folic acid is truly a problem, however, there is enough cause for concern and scientific plausibility to make us shift to the natural form of folate over the unnatural synthetic form for all young women of child bearing age and pregnant mothers. We, unfortunately, will still be exposed to the synthetic form when we consume fortified grain-based foods like bread, cereals and pasta.

As with all things in life where they pertain to our health, when possible stick to the natural variants that are proven safe. There is zero evidence that we could find that natural folate in prenatal doses is dangerous.

Look for high quality brand prenatal vitamins that contain folate or methylfolate. A few good choices are Garden of Life's Vitamin Code Prenatal or Mega Food's Baby and Me.

Blessings to all young women and mothers to be,

Drs. Magryta and Stadler


Folic Acid Study CanadaFolic Acid Study Canada
Blom Study
Linus Pauling Institute
Folic Acid and Autism
DHFR and Folic Acid
Folic Acid and Neural Tube Defects
Folate Risk Article
Prenatal Folate vs Folic Acid
Methylfolate vs Folic Acid
Opinion Piece