People taking high doses of the B vitamin folic acid are not at an increased risk of cancer, according to an international analysis - easing some concern about the possible side effects of national programs aimed to raise intake of the vitamin.
The United States and Canada have required flour to be fortified with folic acid since 1998, after deficiencies of it in pregnant women were tied to brain and spinal cord birth defects in their babies.
But fortification isn't required in Western Europe, for example, partly out of concern that the extra folic acid might slightly increase people's risk of cancer due to its role in cell growth. Cells, including cancer cells, need folate - the natural form of folic acid - to grow and divide.
"Folic acid supplementation does not substantially increase or decrease incident of site-specific cancer during the first 5 years of treatment," researchers wrote in The Lancet.
"Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials.
For the analysis, the researchers combined data from 13 separate trials that randomly assigned participants to daily folic acid or a vitamin-free placebo and recorded who went on to develop cancer.
The studies included a total of close to 50,000 volunteers who were followed for just over five years, on average.
During that time, 7.7 percent of people in the folic acid groups, and 7.3 percent in the placebo groups, were diagnosed with any kind of cancer, a difference that could have been due to chance, researchers said.
Likewise, there was no increased risk of individual cancers - including colon, prostate, lung or breast cancer - attributed to folic acid.
Most trials used daily doses of folic acid between 0.5 and 5 milligrams. In the one study that used a much larger dose, 40 mg daily, there was still no difference in cancer diagnoses.
The total daily amount of folic acid through flour fortification is less than 0.5 mg a day for most in the United States. Folic acid is also naturally found in spinach, asparagus, lettuce and other greens, with a recommended daily upper limit of 1.0 mg.
"The conclusion you can make from this is that over a relatively short period of time, there was no significant benefit or harm," said John Baron from the Geisel School of Medicine at Dartmouth in Lebanon, new Hampshire, who worked on the review.
Most cancers take 10 to 20 years to develop, so it's hard to tell from shorter studies like this one if there really is no link or if the researchers didn't follow people for long enough to see an association, whether positive or negative, he added.
The researchers agreed that the study shouldn't be the last work on the potential side effects of folic acid.
For now, said nutrition researcher Joshua Miller of Rutgers University in New Jersey, people might want to avoid piling supplements on top of multivitamins and fortified food.
"People should realize if they're eating breakfast cereals and bread and pastas, they're getting a good amount of folic acid in food," he said. "I think they should try not to exceed the upper limit."