Folic Acid (Folate)
Folic acid has been garnering its share of attention in the past few years, and the future portends more of the same if current research is any indication. The two main areas of interest include the vitamin's protective roles against a devastating birth defect and' heart disease. The former has captured the attention of women and the food industry because of newly passed legislation, while the link to heart disease prevention is continually being strengthened.
Although folate and B12work together, folate has a life of its own. It also has a tongue-twisting name, pteroylglutamic acid, which isn't much of an improvement over some of the first stabs at naming it: vitamin M, vitamin B10 vitamin B11, rhizopterin, and factor SLR. The friendlier name they settled on, folate, indicates that they first isolated it from spinach and figured out that leafy greens were good sources. After haggling over the name, scientists started realizing how important the vitamin is to the body. Through its role in DNA and RNA synthesis, folate helps in the production of many important compounds, including amino acids and cell parts. It's also involved in the metabolism of fat.
After you eat foods that contain folate, intestinal enzymes have to pull off chemical groups called glutamates before the intestine can absorb the vitamin. Some compounds in foods, especially in yeast and legumes, can interfere with the enzymes and reduce absorption. Although any part of the small intestine can absorb folate, the preferred site is the first third of the small intestine. Similar to other nutrients, a variety of intestinal diseases that affect the absorbing cells of the small intestine can cause a folate deficiency, especially in the upper part of the intestine.
Various drugs, such as those used to control epilepsy, can also cause problems with folate absorption. Chronic alcohol abuse often causes folate deficiency for several reasons, one of which is the liver's role in activating folate, as well as alcohol's interference with the intestinal enzymes. Any factor that increases the metabolic rate, such as infection or trauma, will increase the need for folate.
Where's the Folate?
A variety of foods contain folate, and good sources include liver, leafy vegetables, legumes, and whole grains. Although folate occurs in many foods, one difficulty in getting enough folate is that the vitamin is extremely sensitive to heat and other processing methods. Some studies show that up to 95 percent of the folate can be lost by long cooking times and commercial processes such as canning. This may be the reason that surveys show some Americans aren't getting enough of the vitamin, with one recent study reporting that 88 percent of Americans don't meet the RDA.
The National Institute of Medicine recently revised the 1989 RDA in switching to the new DRI and increased the recommended level of folate by twice the amount to 400 micrograms. Interestingly, the 1989 RDA committee had cut the folic acid RDA by half, from the previous level of 400 micrograms! The Institute of Medicine broke new ground and suggested that Americans either take supplements or eat foods that are fortified with the vitamin. Fortified sources include most breakfast cereals and other grain products. Their rationale was based on two facts: dietary surveys show that Americans don't eat enough foods high in folate, and new studies show that the body absorbs twice as much folate in the synthetic form as from the natural form of folate in foods. Food manufacturers use the synthetic form when they fortify food products.
Another important reason for the huge increase in the recommended folate level is the evidence for protection against neural tube defects (NTDs) in newborns. The neural tube is tissue which gives rise to the embryo's brain and spinal cord. Defects of this tube, of which spina bifida is the most common, cause profound disabilities and high risk for infant death. In a recent survey targeting the concern for NTDs, the Centers for Disease Control and Prevention (CDC) reported that only 32 percent of women of childbearing age take folic acid supplements.
Women Need More Folate
Evidence for folic acid's role in preventing NTDs had continued to mount in the late 1980s. Initially, experts thought that women needed to ensure an adequate intake only during pregnancy. But later studies began to suggest that it was actually a woman's prep regnancy folic acid status that was key to the development of NTDs in her newborn. By 1992, the u.s. Public Health Service recommended that all women of childbearing age consume 400 micrograms of folate daily to reduce their risk for bearing a child with NTDs. The agency had projected that of the nearly 4,000 annual cases of the disease, half could be prevented by adequate folic acid intake.
In response, the Food and Drug Administration (FDA) issued a proposal and three final rules in March 1996. These included a requirement for folic acid fortification of many enriched grain products and authorization for specific health claims. A food item meeting the FDA criteria for "good source" can make the health claim regarding NTDs. One constraint is that a food item containing folate and also 100 percent of the RDAfor vitamins A and D cannot use the health claim because of A and D's adverse effects on fetal health.
By January 1998, the requirement for folic acid fortification of enriched grain products took effect. All commercial grain products have to be enriched with between 430 micrograms and 1,400 micrograms perpound. Breakfast cereals may contain up to a daily dose of folic acid. Examples of the types of grain products covered by the requirement include flour, self-rising flour, corn grits, cornmeal, farina, rice, macaroni products, noodles, breads, rolls, and buns. The FDA is concerned about some people getting too much folate because of food fortification. The existing food additive regulation wouldn't have been able to prevent excessive intakes because it permitted the addition of folic acid to virtually any food, so the FDA amended the regulation.
What About Men?
The folate focus had been almost exclusively on women, until some intriguing studies began to link the vitamin with heart disease. The evidence that folate lowers homocysteine, and therefore heart disease risk (CHD), is strong-strong enough that experts are now reminding men that they need folate, too. Early work on the relationship between CHD and homocysteine suggested that three B vitamins were helpful in reducing blood levels of this risk factor, but it wasn't clear which of the trio was responsible. In 1995, researchers at the University of Washington reported on their meta-analysis of thirtyeight CHD and folic acid studies. Based on their analysis, they projected that increasing the American intake of the vitamin could prevent 56,000 CHD deaths annually.
More evidence on folic acid's protection against CHD came recently from a study at the Cancer Bureau in Ottawa, Ontario. Canadian researchers examined blood levels of folic acid collected from over 5,000 people in 1970. The prospective study showed that subjects with the lowest blood levels of the vitamin were 69 percent more likely to die of CHD in subsequent years. But remember the caveat about the strength of a research study: even if epidemiologic studies show a link, it may not be causal. The proof of the connection can only come from an intervention or clinical trial.
Proof came fast! Within the span of six months, a spate of converging studies crowned folate as the unequivocal champ in the fight against CHD, relegating its B brethren to the stage wings. The most recent of these studies came from the Dutch researchers mentioned in the B12section which supported the homocysteine-lowering effect of the three Bs, but also showed that folate could go it alone.
Other studies included a study from Ireland in which researchers gave thirty healthy men varying doses of folate for six weeks, checking homocysteine levels throughout. Folate effectively lowered homocysteine in all groups except the group with already low levels of the risky compound. They found that 200 micrograms was the most effective dose, compared to 100 and 400 micrograms. This was good news, since there is less concern for toxicity when the supplement is a lower dose but still effective.
With the recent legislation mandating food fortification and consumers taking supplements to get the vitamin's purported protective effects, the FDA's concern about people getting too much folate is shared by others. In a review of vitamin toxicity, one expert put the concern in perspective. His review stated that the three main concerns regarding folate safety are masking pernicious anemia, interference with zinc function, and interference with certain medications.
As for the first, studies show that only doses exceeding 5,000 micrograms can mask the anemia, and those studies used injections, not oral supplements. The second concern for zinc is more problematic. Folate does seem to interfere with the body's use of this important mineral, based on lab studies. But the proof again has to come from intervention studies, and large clinical trials using the recommended 400 microgram or slightly higher dose through pregnancy don't show problems with zinc. Furthermore, the reviewer points to the large body of evidence showing "clear benefit in reducing risk of NTDs."
As for folate's interference with certain medications, two drugs are of concern-an antiepilepsy drug, diphenylhydantoin, and a chemotherapy drug, methotrexate. The review concludes that studies show that folate can reduce diphenylhydantoin's effectiveness in controlling seizures, but the doses used were from 5,000 to 30,000 micrograms. Interestingly, for methotrexate, recent studies show that a 1,000 microgram folate supplement actually reduced the drug's toxic effects without reducing its overall effectiveness.