In nature, there is a family of folates naturally occurring in various foods. Like other natural vitamins, they are biologically active as coenzymes in the body, helping many vital reactions in the prevention of diseases, including:
- Cancer. This is one of the conditions that natural folates help prevent, as studies have long shown.
- Cardiovascular disease. Folate helps the body regulate a substance called homocysteine. While studies show that dietary folate reduces the risk of cardiovascular disease, the same cannot be said of synthetic folic acid. In an evaluation of previous studies, Lydia Bazzano and colleagues at Tulane University School of Public Health (JAMA 2006;296) concluded that, “Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases.”
- Depression and other brain disorders including cognitive dysfunction such as Alzheimer’s disease, can also be prevented and treated by natural folates. However, with few exceptions, dietary supplements of synthetic folic acid have not been shown to accomplish these feats.
Folate Vs. Folic Acid
It’s important to differentiate between natural folates in foods, and synthetic folic acid in vitamin pills and fortified processed foods. By convention, the term “folic acid” refers specifically to the synthetic form of the vitamin. Chemically, it’s fully oxidized, a non-coenzyme, and inactive because it can’t be used in this form by the body. This compound is used in dietary supplements and fortified foods, because it’s cheap and very stable.
It’s been theorized that the cause of so many folate-related genetic polymorphisms today is high levels of unmetabolized folic acid (UFA) from high intakes of synthetic folic acid. In animal studies, higher levels of UFA can adversely affect DNA, and these changes influence subsequent generations. There is concern that the same problem is occurring in humans. In Spain, for example, the prevalence of the polymorphism has reportedly doubled since the introduction in 1982 of folic acid supplements for women in early pregnancy.
It has now been years since researchers started questioning the use of fortification of folic acid at such high levels, and the possible genetic and disease consequences. According to the U.S. Institute of Medicine, a safe upper limit of folic acid intake is 1,000 mcg for adults and 300-800 mcg for children, depending on age. However, there is no consensus about what blood concentrations of unmetabolized folic acid might cause harm (this form is due to the inability of the body to convert synthetic folic acid to a natural form). According to research, the upper limit of safety appears to be around 59 nmol/L.
Synthetic folic acid may actually reduce the body’s ability to metabolize food folates, and prevent the conversion of folic acid to its most active form, 5-MTHF.
Unfortunately, many people are unable to convert folic acid to the natural active form due to a genetic disorder. This problem could also increase UFA.
Once inside the body, all forms of this vitamin — the food folates and folic acid — are converted to the most metabolically active folate called 5-methyltetrahydrofolate or 5-MTHF. The intestines and liver play the key roles in enabling this process. Recent studies show that the liver is limited in its ability to metabolize folic acid in oral doses greater than 260 to 280 mcg. Amounts beyond this can overwhelm the body’s metabolism, according to researchers, resulting in unmetabolized folic acid, or UFA.
Dangers of Folic Acid
In the case of folic acid, if conversion to 5-MTHF does not occur effectively, which can take place when too much of the synthetic form is consumed, UFA can accumulate in the blood. While this may be a marker that excess synthetic and or fortified foods have been consumed, UFA is associated with a variety of potential health problems. These include:
- Impairment of the body’s production of natural killer cells weakening the immune system. Natural killer cells are an important part of our body’s immune response, capable of killing tumor cells and viruses, for example. (It’s now known that natural folate can also act as a powerful antioxidant).
- High folic acid intake may increase the risk of cognitive decline with aging. A recent study by Martha Savaria Morris and colleagues at Tufts University (Am J Clin Nutr;2010, 91) showed a relationship between UFA and lower cognitive test scores in subjects 60 years and older.
- This study also showed that those consuming alcoholic beverages combined with circulating UFA can interact synergistically to precipitate anemia even in the absence of vitamin B12 deficiency. This translates to nearly two million elderly who might be at increased risk of cognitive impairment.
- In pregnant women, high folic acid in the blood may increase the risk of insulin resistance and obesity in their children.
This means that, despite consuming enough folic acid from fortified food or synthetic dietary supplements, deficiency can commonly occur, even if blood levels of folic acid are normal. Knowing whether you, your partner or your children have this polymorphism is accomplished with a simple blood test (discussed below).
The polymorphism has not only become common, but its incidence is rising rapidly in some populations. The cause appears to be environmental.
Those with the highest blood concentrations of folic acid are children aged 5 years and under. While 43 percent of these children had blood concentrations approaching the limit of 50, 10 percent had levels above 77. This is astonishing, and reflects intake of junk food, high in fortified synthetic folic acid.
The intake of folic acid needed to achieve these blood levels has been estimated by researchers. Forty-three percent of children 5 years and older are consuming in excess of 780 mcg of synthetic folic acid each day. This is double the proposed tolerable upper limit (300-400 mcg) for children of that age. Even more alarming is that 10 percent are consuming more than 1,320 mcg per day, which is well above the tolerable upper limit for adults. High levels were also found in children aged 6-11 years, and those over the age of 60. The potential harm is a particular problem in children who are at a rapid stage of development when susceptibility to genetic damage is high. In addition, a mother’s folate status can influence the child’s genes.