The Critical Role Played by Folic Acid

Folic acid is the synthetic version of the nutrient folate, a part of the B-complex group of vitamins (i.e., B-9). It is a water-soluble vitamin, which means that it is not stored in the body within fat cells or other tissues, and therefore must be replenished daily. Folate is a necessary nutrient in the human body for the health of red blood cells.

A Short History of Folic Acid
In 1931, while in India, a health researcher named Lucy Wills observed the effect of liver and yeast extracts on tropical macrocytic anemia and concluded that this disorder was due to a dietary deficiency. Wills determined that the curative power of the substance in yeast was equal to the same curative power in liver. The substance in the yeast was originally referred to as vitamin M, but in later years, the name folic acid was suggested, using the Latin term folium (leaf) due to the fact that spinach was found to contain high levels of the nutrient.

Anemia is a condition resulting from insufficient hemoglobin in red blood cells required to carry the necessary amount of oxygen to cells and tissues. This condition may result from a wide variety of medical issues, including folate deficiency. In the presence of folate deficiency, the body often creates large red blood cells that do not contain adequate hemoglobin, the substance in red blood cells that carries oxygen to your body’s cells.

In 1996, the Food and Drug Administration published regulations requiring breads, cereals, flours, corn meals, pastas, rice, and other grain products to be enriched with folic acid. Grains and cereals form a significant large part of the American diet, so these products have, by default; become the average American’s source for folic acid.

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Animal? Mineral? Vegetable? – How Should I Take Folic Acid?
The Recommended Daily Allowance (RDA) for folate is listed as Dietary Folate Equivalent (DFE), which accounts for the differences in absorption of naturally occurring folate and the synthetic folic acid.

Due to their differences, folate and folic acid have different absorption rates. The average rate of absorption for folate is 50 percent, for folic acid, it is 100 percent, while the same folate found in foods is absorbed at a rate of 85 percent. Fortified foods contain proteins as a binding agent for the folic acid. The folic acid has to be released from the food by enzymes before it can be absorbed, hence impacting its absorption rate.

This raises the question of supplementation. Is it better to obtain folate through food or to supplement with folic acid?
Naturopath Melissa Peterson writes: “The folate food form has many glutamate molecules attached. Enzymes in the intestine have to remove these glutamate molecules until there is only one left, before folate can be absorbed into the bloodstream. Additionally, the following factors may slow down food folate absorption and negatively affect the benefit of folate from foods: a deficiency in the mineral zinc—the enzymes are dependent on zinc; excess intake of foods such as legumes, cabbages and oranges—these contain enzyme inhibitors; chronic alcohol ingestion”.

Supplemental folic acid on the other hand only has one glutamate molecule attached and is not affected by the above factors.

What is the RDA for Folic Acid?
The Centers for Disease Control and Prevention (CDC) state that a healthy woman requires 400 micrograms (mcg) of folic acid each day, even if they are not planning a pregnancy. The NIH provides the following recommendation for pregnant women and folic acid intake: “Folic acid is very important for all women who may become pregnant. Adequate folate intake during the periconceptual period, the time just before and just after a woman becomes pregnant, protects against neural tube defects. Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthful diet prior to and during the first month following conception. Since January 1, 1998, data suggest that there has been a significant reduction in neural tube birth defects. Women who could become pregnant are advised to eat foods fortified with folic acid or take a folic acid supplement in addition to eating folate-rich foods to reduce the risk of some serious birth defects. For this population, researchers recommend a daily intake of 400 mcg of synthetic folic acid per day from fortified foods and/or dietary supplements.”

According to the Institute of Medicine, National Academy of Sciences, teenage boys (14 – 18) and men aged 19 and up, should consume 400 mcg of folic acid daily. Folate may be important for men’s reproductive health and has been associated with higher sperm counts and density.
Medical conditions that increase the need for folic acid or result in increased loss of folic acid include:

* Pregnancy and lactation (breastfeeding)
* Alcohol abuse
* Malabsorption
* Kidney dialysis
* Liver disease
* Certain anemias

Additional purported benefits of folic acid supplementation include the prevention of isolated systolic hypertension, and the reduction in risk of stroke amongst certain groups, possible due to the impact upon hypertension. There are some preliminary studies showing the potential correlation between the consumption of folic acid and the reduced risk of esophageal, stomach, and ovarian cancers, but more studies are required before a definitive causal connection may be established. Furthermore, there is the potential that individual who currently suffer from these types of cancers may actually worsen their conditions by consuming this substance.

Potential Contraindications for Supplementation with Folic Acid
The NIH also lists the following medications that interfere with folate utilization:

* Anticonvulsant medications (such as dilantin, phenytoin and primidone)
* Metformin (sometimes prescribed to control blood sugar in type 2 diabetes)
* Sulfasalazine (used to control inflammation associated with Crohn’s disease and ulcerative colitis)
* Triamterene (a diuretic)
* Methotrexate (used for cancer and other diseases such as rheumatoid arthritis)
* Barbituates (used as sedatives)

Other interactions should be monitored when supplementing with folic acid. Intake of supplemental folic acid should not exceed 1,000 mcg per day to prevent folic acid from triggering symptoms of vitamin B12 deficiency. Folic acid supplements can correct the anemia associated with vitamin B12 deficiency, however it will not correct changes in the nervous system that result from vitamin B12 deficiency. Permanent nerve damage may result if vitamin B12 deficiency is not treated.

Conflicting Studies
Again, the studies continue to yield conflicting results: (i) folate supplementation has been shown to reduce the risk of colorectal cancer, however, the results of a 2007 randomized clinical trial noted that colorectal adenomas were not impacted; (ii) a 2006 study of 81,922 Swedish adults found a correlation between reduced risk of pancreatic cancer and folate from whole foods as opposed to supplements; (iii) contradictory results have been found with respect to the prevention of breast cancer, and (iv) ironically, folic acid supplementation appears to double the risk of prostate cancer in men.

Potential Benefits Requiring Additional Studies
There is some limited promising evidence showing a correlation between depression and low folate levels, while a study published in 2007 in the Lancet, reported on a three year study of individuals over the age of 50 who reported enhanced short-term memory, cognitive agility, and verbal fluency after daily supplementation with 800 micrograms of folic acid daily.

Significant Issues Associated with Prolonged Folate Deficiency
The signs of folate deficiency are sometimes subtle, but include digestive disorders such as diarrhea; loss of appetite; weight loss; weakness; sore tongue; headaches; heart palpitations; irritability;  forgetfulness; and behavioral disorders. Higher homocysteine levels in the blood, a risk factor for cardiovascular disease, also may result from folate deficiency.

Different groups are at risk for various concerns with respect to the consequences of folate deficiency:

•    Newborns – low birth weight, premature, and/or infants with neural tube defects.
•    Infants and children – slowed overall growth rate.
•    Adults – a particular type of anemia can result from long-term folate deficiency.

Conclusion
Sufficient evidence exists as to the benefits of folic acid supplementation; however, the absence of definitive studies suggest that individuals should not exceed the recommended RDA of 400 mcg without the prior approval of their physician, and this substance is best used as part of a premium multivitamin/mineral complex to ensure that other nutrients designed to enhance the bioavailability of this substance are present.

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