BioEd Online

The widespread practice of fortifying food with folic acid could be slowly changing the genetic make-up of the population - and perhaps creating future generations more vulnerable to fatal diseases.

That's the provocative idea being proposed by researcher Mark Lucock of the University of Newcastle in Ourimbah, Australia, and Zoe Yates of the University of Leeds, UK, in Nature Reviews Genetics¹.

Folic acid is a type of B vitamin that is vital for many metabolic processes, and it is added by law to flour and grain products in some countries, including the United States. This ensures that pregnant women, who are often unaware of their pregnancy early on, eat enough folic acid to reduce the risk of their babies developing defects in the brain and spine.

Lucock and Yates propose that folic-acid fortification, which bumps up the entire population's intake of the nutrient, could slowly and inadvertently change the genetic make-up of the population and potentially make us unhealthier as a whole. Lucock says this idea has not been widely discussed by scientists before.

Gene variant

The researchers point to a small collection of studies showing that the babies of women on diets rich in folic acid tend carry a particular form of a gene involved in metabolizing the vitamin, called 677T MTHFR, than the children of women who did not receive adequate folic acid. A study from 2000, for example, showed that babies were four times more likely to carry this gene variation than were fetuses that were miscarried².

Such studies suggest that fetuses carrying this gene variant are more likely to survive to birth, if their mothers are getting an adequate or abundant intake of folic acid. And because widespread folic-acid fortification and vitamin supplements ensure that more and more mothers do indeed get high levels of the nutrient, the number of children carrying this variant could be climbing.

This change of genetics could have a negative effect on health over time, Lucock suggests. Several studies have shown that this same form of the gene, 677T MTHFR, may increase the risk of various conditions in adults, including heart disease, certain forms of cancer and complications of pregnancy.

Dependent population

Some studies suggest that these harmful effects of the gene are more common when people's diets are low in folic acid. It's not clear why this might be, but as long as people's diets remain high in folic acid, Lucock proposes, this would compensate for any adverse impacts of 677T MTHFR.

However he warns that widespread fortification could effectively create a future population that is artificially dependent on copious quantities of the vitamin - and one that would be more vulnerable to certain fatal diseases if that supply vanished.

At present, Lucock believes that the health benefits of folic-acid fortification for pregnant women outweigh the potential future risk. But until the potential health risks of fortification are clearer, he suggests that governments could consider lowering their recommendation on how much folic acid should be added to food. They might, for example, aim for women to obtain 200 micrograms per day rather than the 400 micrograms currently recommended in the United States.

Other nutrition researchers say there is not yet enough evidence to say whether or not this genetic selection is taking place. "It's an interesting hypothesis and worth looking at - but it has not been fully established," says Jesse Gregory, who works on folic acid at the University of Florida, Gainesville.

And human geneticist Larry Brody at the National Human Genome Research Institute in Bethesda, Maryland, says that folic-acid fortification would change the genetics of the population so slowly that the effects would never be seen. "It would probably take a couple of thousand years," he says. "It's not in touch with reality."

Good, bad and ugly

Besides preventing spinal-cord defects in babies, some studies suggest that folic acid also protects against heart disease and stroke. But the long-term safety implications of boosting folic acid are unknown. There are fears that high doses might accelerate the progression of certain cancers, for example.

Concerns such as these have prevented many countries, such as the United Kingdom, from mandating that the nutrient be added to flour. "In many ways the rest of the world is waiting on the outcome of what is a public-health experiment [in the United States]," Gregory says.

Lucock and other researchers want longer studies to evaluate the possible long-term risks of folic-acid fortification, and some such studies are already under way. "I don't think we'll have the [results] for another few years," says Irwin Rosenberg, a nutritionist at Tufts University in Boston.