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Frankenstein Folic Acid?

You see folic acid on a lot of the packages of foods you eat-cereals, pasta, and other fortified foods. It is also a typical ingredient in lesser quality supplements like multivitamins and B complex.

Many individuals, including non-nutritionally oriented physicians, are surprised that folic acid is a synthetic type 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 man-made, not God-made.

In 1998, there was a mandatory folic acid fortification of cereal grain products to decrease the incidence of neural tube defects in infants. The mandatory folic acid enrichment of grain goods has nearly eliminated dietary folate deficiency and reduced the rate of neural tube defects in North America. The U.S. Food and Drug Administration mandated manufacturers to include 140 mcg of folic acid per 100 grams of enriched bread, cereals, flours, cornmeal, pasta, rice, and other grain goods. Folic acid is used in food enrichment due to its chemical stability and good bioavailability.

Questions About Cancer

One problem that has increased controversy is that the published literature shows that while dietary folate deficiency is associated with increased cancer risk, so is excessive folic acid supplementation!

There is worry over the high consumption of folic acid in North Americans due to the enrichment of grains, dietary supplements, energy drinks, and medications. For instance, Henry et al. report that breakfast cereals include 160-175% over reported levels, and people regularly eat more than the recommended serving sizes. Furthermore, it is not unusual for women of childbearing age to supplement folic acid above the 1000 mcg/day limit. 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.

As stated before, published literature demonstrates that reduced folate status promotes cancer, particularly colorectal cancer. Yet data also exists regarding raised folate levels and the promotion of tumor formation from preexisting cancers. However, the research is mixed and requires ongoing study.

Folic acid has to be converted into an active form known as tetrahydrofolate (THF). The enzyme that is needed for this conversion, called 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 decrease in natural folate cell receptor activity. Folate participates in many responses in the body, including normal cell division. Studies show that this unusable folic acid is practically ubiquitous in the serum samples of all Americans. The impacts of raised UMFA or folic acid levels are not known, but research has identified possible adverse effects, although the studies are inconclusive.

Folate or methylfolate metabolism is different in that it is converted right to THF and then the active circulating form known as 5-methyltetrahydrofolate (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 variants in treating depression in the journal Alternative Therapies.

Recent research has shown that specific population segments might be at greater risk for possible adverse effects from raised folate status. These population groups include pregnant women who go beyond the upper limit of folic acid at 1000 mcg daily. Data shows 33% of pregnant U.S. women exceed 1000 mcg daily, 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 need for folate intake. The need for folate during pregnancy increases up to 10-fold, and a deficiency can cause congenital abnormalities. Additionally, kids are vulnerable to the possible adverse effects of excess folic acid, particularly for those who regularly take vitamin supplements where over half exceed the upper limit.

Reasons for Folate Deficiency

  • Poor dietary intake (uncommon)
  • Malabsorption (e.g., Crohn's disease)
  • Chronic alcohol addiction
  • Increased needs (pregnancy, lactation, hemodialysis)
  • Deficiencies of cofactors such as B12 and zinc.
  • Genetic factors (MTHFR polymorphisms and others)

My Recommendations

I suggest avoiding supplements that contain folic acid. Many people consume folic acid due to the plethora of enriched foods and sub quality supplements. Additionally, many individuals have genetic variations where they do not metabolize folic acid effectively. You also read in this article that all people have weak enzyme activity converting folic acid into the active, usable form referred to as THF.

Use supplements that include folate or methylfolate, the type found in foods that your body can convert into a usable form. Prenatals, multivitamins, children's vitamins, B complex formulas, and other dietary supplements are available that include the natural folate form and not folic acid. The products at our clinic and do not have folic acid but rather use the nature-identical methylfolate. Unfortunately, it is highly probable that your doctor is not educated on the possible problems with folic acid. Therefore, work with a nutrition-trained physician when using supplements.

Lastly, make sure not to overload your body with folate, particularly folic acid.

Recommended Dietary Allowances (RDAs) for Folate

*Adequate Intake (AI)Table from NIH Folate Fact Sheet for Health Professionals