Folate is a form of naturally occurring folic acid in the body. Folic acid is also known as vitamin B9, vitamin Bc or folacin.
Vitamin B9 (folic acid and folate inclusive) is essential to numerous bodily functions. The human body needs folate to synthesize, repair and methylate DNA as well as to act as a cofactor in biological reactions involving folate. Folate was isolated in 1941 from spinach and named after the Latin word folium (= leaf). Although the initial impetus for research on folate metabolism was to find a cure for anemia, it was soon recognized that the administration of folate enhanced the growth of existing tumors and that folate metabolism may be a promising target for anticancer drug design.
A lack of dietary folic acid leads to folate deficiency, which is uncommon in normal Western diet. This deficiency can result in many health problems, the most notable one being neural tube defects in developing embryos. However, a complete lack of dietary folate takes months before deficiency develops, as normal individuals have about 500–20,000 µg of folate in body stores. Common symptoms of folate deficiency include diarrhea, macrocytic anemia with weakness or shortness of breath, nerve damage with weakness and limb numbness (peripheral neuropathy), pregnancy complications, mental confusion, forgetfulness or other cognitive declines, mental depression, sore or swollen tongue, peptic or mouth ulcers, headaches, heart palpitations, irritability, and behavioral disorders. Low levels of folate can also lead to homocysteine accumulation. DNA synthesis and repair are impaired and this could lead to cancer development.
Folate is now commonly used by food producers to fortify our diet, normally in grain products. In the United States, the Food and Drug Administration mandated the folate fortification of grain products in January 1998 and it was also implemented in Canada. The primary driving force behind this policy was the recognition that periconceptional folate supplementation in addition to normal dietary folate intake significantly reduced the incidence of neural tube defects (NTDs), one of the most common birth defects.
Initial data suggest that this public health measure was successful, resulting in a substantial reduction in the prevalence of neural tube defects.
Although these reports were reassuring in that the population fraction with low serum folate was minimized (from 16% to 0.5%; ref. 16), they also raised concerns that fortification exceeded the original daily intake target by as much as 2-fold (17-19). This intake of folic acid from fortified food (f100 to 200 Ag/d) coincides today with high consumption of nutritional supplements in the U.S. population (f400 Ag/standard multivitamin) as well as increased availability and marketing of nutrition bars, drinks, and other fortified foods (often supplemented at 400 Ag/serving), resulting in a markedly elevated intake of folic acid in the population from multiple sources (http://cebp.aacrjournals.org/content/15/2/189.full.pdf).
Food fortification rather than supplementation in planning pregnancies was deemed necessary because:
1. There is a perceived failure of public health efforts to influence those persons most at risk
2. The neural tube closes during the fourth week of gestation, a time when many women are unaware of their pregnancy.
3. Due to concerns that folate fortification may mask symptoms of vitamin B-12 deficiency, primarily in the elderly population, the level of fortification chosen was estimated to provide on average 100 µg additional folic acid daily with only a very small proportion of the population receiving >1 mg. The upper limit of 1 mg was a round number chosen by the Institute of Medicine (IOM) as unlikely to produce masking, although the folate intake that produces masking is controversial, with some arguing that intakes <1 mg may cause this effect. (http://www.ajcn.org/content/77/1/8.full)
However other studies suggest that the maximum benefit of fortification has already been achieved. Over the past few years, the US population has been exposed to a significant increase in folate intake, for which there are essentially no data on safety.
Folic acid is generally regarded as safe, but there is concern that folic acid fortification may have adverse effects in subpopulation groups not originally targeted for fortification. In this regard, an emerging body of evidence suggests that folic acid supplementation may enhance the development and progression of already existing, undiagnosed premalignant and malignant lesions.
The accumulation of good news—ranging from the established reduction of neural tube defects to the putative prevention of several types of cancer, cardiovascular disease, and possibly dementia—has made it seem that folate is a ‘‘wonder drug’’ that is not only inexpensive, but also safe for use as a chemopreventive agent.
However, recent research on the effect of this nutrient on animal shows that folate could be detrimental to human health and could even cause cancer. Although research to date supports several of these claims, these warnings have appeared to be true, challenging us to adopt a more nuanced view of folate use and raising the need for investigations of the potential health hazards of excessive intakes.
Recent data also suggest the need to distinguish between naturally occurring folates and folic acid, the synthetic form added to supplements and fortified foods. This further complicates the already complex story of folate as a potent vitamin. The potential masking effect of folate on vitamin B-12 deficiency is not only a traditional measure of toxicity, it is a very serious concern from a public health viewpoint because of the high prevalence of vitamin B-12 malabsorption in the elderly.
