Joel Mason, MD
Joel Mason, MD, director of the Vitamins and Carcinogenesis Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston.
Where a little may be good, a lot may be hazardous…such may be the case with folate, and its synthetic form folic acid, the B vitamin that helps protect the nervous system and prevent anemia. For years now, the US government (along with Canada and Chile) has required that most breads, flours, cornmeal, rice and some other grains be fortified with folic acid as a way to reduce birth defects known to be caused by folate deficiency.
It’s working—incidence of neural tube birth defects has been reduced by as much as 50% in these countries, but at the same time, there has been another, totally unexpected development. All three countries have also seen rates of colorectal cancer rise, an abrupt reversal after years of decline—with the increase estimated at an additional four to six cases of colorectal cancer per 100,000 people. Adding to that concern were the results of a large clinical trial published in the Journal of the American Medical Association in 2007 concerning folic acid supplementation and colon cancer. The participants, all of whom had previously had colon polyps, were divided into two groups—one group took 1,000 mcg daily (this is considered the uppermost safe limit and exceeds the daily recommended intake, which is 400 mcg) of folic acid and the other a placebo. After seven years, the study found that those taking supplemental folic acid were more likely to have multiple polyps, and at higher risk, than those who didn’t take it. Even more troubling: A follow-up study of this same group found that after 10 or 11 years, those supplementing with folic acid had a three-fold increase in prostate cancer compared with the group on placebo.
Joel Mason, MD, director of the Vitamins and Carcinogenesis Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, is author of a recent report on this topic in Nutrition Reviews. He told me the report generated controversy because folate fortification has so effectively reduced birth defects—but his intent, however, was not to be “anti-fortification,” but rather to generate dialogue about a potential risk for one group of people in spite of the clear benefits for another at a time when many countries are considering fortification.
Paradoxically, there is sound evidence that folate, which has a pivotal role in DNA synthesis, protects against colorectal cancer. Dr. Mason speculated that perhaps its very function of helping create DNA for new cells means that when ingested in large quantities, folate stimulates the growth of existing cancerous or precancerous cells that would otherwise remain stable. Another possibility relates to the fact that folic acid, rather than folate itself, is used to fortify foods because it is cheaper and also more stable. The body must convert folic acid into folate, he says, and ingesting an excessive amount of folic acid may overwhelm the conversion system, leaving a reservoir of synthetic folate that could have detrimental effects. Current research is exploring whether folic acid itself is cancer-promoting, but there’s little evidence of this Dr. Mason said, so he believes it’s more likely related to excessive intake of the vitamin, regardless of its form.
In no way does this diminish the importance of an abundance of folate, says Dr. Mason, describing it as “healthful and in no way harmful.” Dietary folate is available in a variety of foods, including dark green leafy vegetables, legumes, citrus fruits and berries.
And folic acid, for the most part, also is healthful and relatively few people are at risk for getting too much. Dr. Mason says supplementation adds a “fairly modest amount” to typical intake, about 100 mcg to 200 mcg per day. He noted that the situation only gets worrisome for those who routinely exceed 1 mg a day (1,000 mcg) of folic acid through supplementation in a variety of forms. This would describe a person who takes a multivitamin (400 mcg of folic acid), a B complex (another 400 mcg), and then eats fortified breakfast cereal (typically containing 100 to 400 mcg). It’s still morning and we already are at the ceiling of 1,000 mcg folic acid—but then for lunch there is a sandwich with fortified bread (50 to 120 mcg for two slices), maybe a pasta dinner (another 100 to 200 mcg) and the total is nearly 1,400 mcg, clearly topping the upper limit of safety. For those who snack on vitamin-packed energy bars and sip vitamin-infused water all day, the folic acid intake goes even higher.
There isn’t enough data yet to make an absolute statement about folic acid intake, but the current recommendation regarding the uppermost safe intake level (1,000 mcg/day) continues to be an excellent guideline, Dr. Mason said. Vitamin labels clearly identify how much folic acid they contain, but it’s harder to figure out how much is in fortified foods. The law says that all wheat flour, rice and several other uncooked cereal grains labeled as “fortified” must have added folic acid…but there are a few nonfortified examples of these foods on the market. You can look for these, but it might be easier to just be aware of how much folic acid you are ingesting in vitamin supplements, because these appear to be the major source of excessive intake.