Frankenstein Folic Acid?

You see folic acid on many of the packages of foods you eat-cereals, pasta, and other fortified foods. It is also a common ingredient in lesser quality supplements such as multivitamins and B complex.
Many people, including non-nutritionally oriented doctors, are surprised that folic acid is a synthetic version of naturally occurring folates found in dark green leafy vegetables, fruits, nuts, beans, peas, seafood, eggs, grains, dairy, and meat. In other words, folic acid is artificial, not God-made.
In 1998, there was a mandatory folic acid fortification of cereal grain products to reduce the incidence of neural tube defects in newborns. The mandatory folic acid enrichment of grain products has nearly eliminated dietary folate deficiency and reduced the rate of neural tube defects in North America. The U.S. Food and Drug Administration required manufacturers to add 140 mcg of folic acid per 100 grams of enriched bread, cereals, flours, cornmeal, pasta, rice, and other grain products. Folic acid is used in food enrichment due to its chemical stability and good bioavailability.
Questions About Cancer
One issue that has raised controversy is that the published literature demonstrates that while dietary folate deficiency is associated with increased cancer risk, so is excessive folic acid supplementation!
There is concern over the high intake of folic acid in North Americans due to the enrichment of grains, dietary supplements, energy drinks, and medications.2 For example, Henry et al. report that breakfast cereals contain 160-175% over reported levels, and people often consume more than the suggested serving sizes.In addition, it is not uncommon for women of childbearing age to supplement folic acid above the 1000 mcg/day limit.2 The Recommended Dietary Allowance (RDA) for adults 19 years and older is 400 mcg of dietary folate equivalents (DFE), 600 mcg DFE for pregnancy, and 500 mcg DFE for lactation.3
As mentioned earlier, published literature demonstrates that low folate status promotes cancer, especially colorectal cancer.4 Yet data also exists regarding elevated folate levels and the promotion of tumor formation from preexisting cancers. However, the research is mixed and requires ongoing study.
Folic acid must be converted into an active form known as tetrahydrofolate (THF). The enzyme that is required for this conversion, known as dihydrofolate reductase (DHFR), has low activity in humans to perform this function. As a result, there is an accumulation of un-metabolized folic acid in the blood and tissues. This unusable folic acid competes with the natural folate receptors in the cells, so there is a reduction in natural folate cell receptor activity. Folate participates in many reactions in the body, including normal cell division. Studies show that this unusable folic acid is nearly ubiquitous in the serum samples of all Americans. The effects of elevated UMFA or folic acid levels are unknown, but research has identified possible adverse outcomes, although the studies are inconclusive.
Folate or methylfolate metabolism is different in that it is converted directly to THF and then the active circulating form known as 5-methyl tetrahydrofolate (5-MTHF).
The diagram below shows the challenges of converting folic acid into the active 5-MTHF, whereas folate (methylfolate) is directly converted into 5-MTHF. This diagram was taken from an article I published on the role of folate and genetic variations in treating depression in the journal Alternative Therapies.

Stengler M. The Role of Folate and MTHFR Polymorphisms in the Treatment of Depression. Altern Ther Health Med. 2021;27(2):53-57.

Recent research has shown that specific population segments may be at higher risk for potential adverse effects from elevated folate status. These population groups include pregnant women who exceed the upper limit of folic acid at 1000 mcg per day. Data shows 33% of pregnant U.S. women exceed 1000 mcg per day, while the number increases to 47% for women who take supplements. To make matters complicated, 40% of U.S. women of reproductive age do not meet their requirement for folate intake. The need for folate during pregnancy increases up to 10-fold, and a deficiency can result in congenital abnormalities. In addition, children are vulnerable to the potential adverse effects of excess folic acid, especially for those who regularly use vitamin supplements where more than half exceed the upper limit.
Reasons For Folate Deficiency
  • Inadequate dietary intake (uncommon)
  • Malabsorption (e.g., Crohn’s disease)
  • Chronic alcoholism
  • Increased requirements (pregnancy, lactation, hemodialysis)
  • Deficiencies of cofactors such as B12 and zinc
  • Genetic factors (MTHFR polymorphisms and others).
My Recommendations
I recommend avoiding supplements that contain folic acid. Many people consume folic acid due to the abundance of enriched foods and sub quality supplements. Also, many people have genetic variations where they do not metabolize folic acid efficiently. You also read in this article that all people have weak enzyme activity converting folic acid into the active, useable form known as THF.
Use supplements that contain folate or methylfolate, the type found in foods that your body can convert into a useable form. Prenatals, multivitamins, children’s vitamins, B complex formulas, and other dietary supplements are available that contain the natural folate form and not folic acid. The products at our clinic and  do not contain folic acid but instead use the nature-identical methylfolate. Unfortunately, it is highly probable that your doctor is not educated on the potential problems with folic acid. Therefore, work with a nutrition-trained doctor when using supplements.
Lastly, make sure not to overload your body with folate, especially folic acid.

Recommended Dietary Allowances (RDAs) for Folate

Age Male Female Pregnancy Lactation
Birth to 6 months* 65 mcg DFE* 65 mcg DFE*
7–12 months* 80 mcg DFE* 80 mcg DFE*
1–3 years 150 mcg DFE 150 mcg DFE
4–8 years 200 mcg DFE 200 mcg DFE
9–13 years 300 mcg DFE 300 mcg DFE
14–18 years 400 mcg DFE 400 mcg DFE 600 mcg DFE 500 mcg DFE
19+ years 400 mcg DFE 400 mcg DFE 600 mcg DFE 500 mcg DFE
*Adequate Intake (AI)
Table from NIH Folate Fact Sheet for Health Professionals
Castaño-Moreno E, Piñuñuri R, Peñailillo R, Casanello P, Llanos M, Ronco A. Molecular Nutrition. Academic Press; 2020:345-365.
Combs G, McClung J. The Vitamins: Fundamental Aspects In Nutrition And Health. 5th ed. London: Academic Press; 2017.
Henry CJ, Nemkov T, Casás-Selves M, et al. Folate dietary insufficiency and folic acid supplementation similarly impair metabolism and compromise hematopoiesis. Haematologica. 2017;102(12):1985-1994. doi:10.3324/haematol.2017.171074
Maruvada P, Stover P, Mason J et al. Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop. Am J Clin Nutr. 2020;112(5):1390-1403. doi:10.1093/ajcn/nqaa259
Office of Dietary Supplements – Folate.,-According%20to%20data&text=Mean%20dietary%20intakes%20of%20folate,455%20mcg%20DFE%20for%20females. Published 2021. Accessed February 25, 2022.
Field MS, Stover PJ. Safety of folic acid. Ann N Y Acad Sci. 2018;1414(1):59-71. doi:10.1111/nyas.13499