Folic Acid Follies

Pregnant women should stop popping these pills like candy.

Take folic acid, but not too much

No woman who’s expecting, or expecting to expect, can avoid the advice, from any doctor or health site worth its salt: Take folic acid. The vitamin deserves its exalted status. When women take it before and during pregnancy, it reduces the risk of devastating neural-tube defects in the fetus. It’s one of the only things we can do to improve fetal health that is supported by rigorous evidence.

But these days millions of women (and men) are getting high doses of the vitamin—and not because we’re piling our plates with natural sources like  spinach and collard greens. Since the late 1990s, the United States has  fortified  many breads, cereals, and pastas with folic acid. And then there are the supplements: both in regular multivitamins and freestanding folic acid pills. For pregnant women, the government recommends a daily dose of 400 micrograms  in addition to any folate, the naturally occurring form of the vitamin. But millions of expectant mothers, as well women who are not yet pregnant,  go hog-wild, taking more than 1,000 micrograms in pill form a day, an amount the government deems the “tolerable upper intake level.” Somewhere along the line, it seems, folic acid crossed the line from vitamin to talisman.

But folic acid is a powerful drug, even if its exact workings remain something of a mystery. For the population at large, it might increase or decrease the risk of certain cancers, depending—perhaps—on whether abnormal cells are already present. A recent mouse study also hints that supplements during pregnancy may boost the risk of breast cancer in the pups (though this has yet to be confirmed in humans). Much of the science here is embryonic, and no reason to shun the vitamin. But there are enough question marks that pregnant women would be smart to stop popping it so freely and to stick to the recommended dose.

The discovery that folic acid could reduce the risk of neural-tube defects was a triumph that has helped to protect millions of babies. In a  randomized clinical trial  published in 1991, British epidemiologist Nicholas Wald proved that pregnant women who took folic acid supplements were less likely to have fetuses with malformations like spina bifida, in which the spinal cord doesn’t develop properly. Since then, because of the fortification of breads, cereals, pastas, and other grains, as well as the emphasis on supplements during pregnancy, the rate of these birth defects has decreased substantially . In the United States today,  about two-thirds of pregnant women  take supplements with folic acid. Yet Americans have never been able to resist too much of a good thing, and this vitamin is no exception. According to Cathrine Hoyo, an epidemiologist at Duke, one worry has long been that too much folic acid can mask deficiencies in vitamin B12, which are associated with anemia and may be linked to cognitive impairment.

But the big debate these days is over the vitamin’s ambiguous relationship to cancer, both in adults and in fetuses. On one hand, a large body of research suggests that getting  adequate amounts  of folate  protects against colon cancer—and possibly prostate cancer, as well. One theory is that the vitamin helps to maintain the integrity of DNA, preventing the kinds of errors that lead to malignancy.

But the story isn’t quite that simple. As early as the 1940s, the legendary oncologist Sydney Farber found that when he gave folic acid to patients with acute leukemia, their cancers proliferated wildly. (Indeed, the first highly effective cancer chemotherapy, which Farber helped to discover, worked by counteracting folate. The anti-cancer drugs  methotrexate  and fluorouracil do the same.) More recently, a paper in the Journal of the American Medical Associationfound that people who had a history of  adenomas, or benign tumors that may become malignant, and who took folic acid supplements did not protect themselves from a recurrence, as some researchers had hypothesized. In fact, they might have increased their risk. The data are still messy, but there’s enough evidence to feel nervous about overdoing it on the supplements, as  this review points out. One theory is that once abnormal cells are present, folic acid may aid and abet their spiraling growth.

This is worrisome for the general population, because abnormal cells creep up on us with age. A large number of older people have precancerous growths in their colons. Similarly, large numbers of older men have abnormalities in their prostates. Many of these will never progress or do any harm. But if it’s true that excess intake of folic acid goads them on, it might actually cause more cases of colon and prostate cancer, says Joel Mason, a professor of medicine and nutrition at Tufts. This would be especially true for older people taking high levels of the vitamin in supplement form. (There’s no evidence that naturally occurring folates in food are harmful, by the way, so kale is not a culprit.)

So what about those pregnant women downing all that extra folic acid? Young women do tend to have lower cancer risk than older people. Certainly their unborn children have had far less time to accumulate precancerous abnormalities than their soon-to-be grandparents. So for those fetuses, we might expect folic acid to reduce the risk of cancer—perhaps by stabilizing the DNA, as researchers think might be the case in healthy adults, as well. This is why a recent study of pregnant mice comes as such a surprise. Canadian researcher Young-In Kim and his colleagues gave pregnant and nursing mice the mouse equivalent of roughly 800 to 1,000 micrograms of folic acid (an amount that many pregnant women today are ingesting daily, above and beyond naturally-occurring sources in food). They then exposed the pups to a chemical known to induce breast cancer. But instead of being more protected, the pups whose moms got folic acid were actually  substantially more likely to develop tumors. No one really knows why this happened—or whether the results will mean anything in people (plenty of cancer studies in mice don’t). But the researchers suggest that folic acid might be altering DNA expression, quieting genes that would otherwise have been protective.

Speculation about folic acid has evolved into its own mini-genre, well beyond these cancer studies. One paper even suggests that too much folic acid for mom might  increase the risk of asthma  for her offspring in early childhood (though the link remains uncertain). The point is not to fan fears that too much of the vitamin is cataclysmic. But a little caution would not be a bad idea. So pregnant women, yes—by all means, take a multivitamin with the recommended amount of folic acid. But don’t also buy fortified drinks and stand-alone folic acid supplements. Spend the money instead on something you could really use: an extra body pillow, perhaps, or a big bottle of Tums.