Time for a Debate on Folate?
Too much of a good thing could turn out to be bad
Six decades ago, Harvard physician Sidney Farber discovered to his disappointment that a synthetic form of the vitamin folate called folic acid, recently shown to prevent cancers in lab animals, actually accelerated the disease in children dying of leukemia. Making good of his inconvenient discovery, Farber went on to develop folate-blocking compounds that became some of the world's first chemotherapies. Separately, other scientists discovered folic acid's tremendous power for good—it prevents birth defects such as spina bifida—and launched a movement to make sure people get enough. But echoes of those early findings have been reverberating of late: New research links widespread use to a surprising rise in colon cancer and perhaps other tumors.
Today, the vitamin is a common food additive throughout North America, and U.S. adults are told to have at least 400 micrograms a day. Since 1998, by government mandate, flour, bread, cereal, pasta, rice, and other grain products have been fortified with folic acid in a campaign to end folate deficiency in childbearing women. Associated birth defects have since fallen by as much as half, from what used to be about 3,000 cases per year in the United States. Folic acid also appears to safeguard some older people against stroke and cognitive decline, and researchers haven't abandoned Farber's original hope that it can stave off cancer. Some manufacturers elect to add it to other foods, too, and many people get an extra dose from a daily vitamin pill.
But some researchers now worry that the vitamin has a dark side. "The [established] benefits are limited to a very specific population—women of childbearing age," says Young-In Kim, a gastroenterologist at the University of Toronto who has studied folate's complex relationship with cancer. "In other groups, it might do more harm than good." Kim and others suspect that folic acid wields "a double-edged sword," as he puts it. Cells use folate to keep their genetic software—their DNA—in good repair and to make copies of DNA when they divide. DNA is less likely to develop the sorts of defects that lead to cancer when it's well maintained, so folate may lower cancer risk in people who are healthy. But once a defect is present, experts theorize, replicating cancer cells hungrily gobble up folate to make new copies of their malevolent DNA. Often, defective cells lurk undetected in outwardly healthy people. "What we've discovered," says Joel Mason, a Tufts University gastroenterologist, "is that folate seems to have a paradoxical effect."
Unintended outcome? The paradox could account for an upward shift in colorectal cancer in both America and Canada in the late '90s. According to Mason's latest research, which appeared in the July issue of Cancer Epidemiology, Biomarkers & Prevention, folic acid fortification may be causing 4 to 6 colorectal cancers annually per 100,000 people—and alternative explanations, such as increasing rates of cancer screening, don't seem to account for the spike. "That works out at 15,000 new cases per year in the U.S.A.," says A. David Smith, a pharmacologist at the University of Oxford in England who advised a British government panel to postpone the country's planned food-fortification policy.
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