Folic acid may raise cancer risk in offspring
From Monday's Globe and Mail
April 20, 2009 at 9:09 AM EDT
Canadian researchers have discovered that folic acid consumed during pregnancy can alter the gene function of offspring, potentially affecting their susceptibility to disease.
The finding is part of a growing - and controversial - body of research that raises serious questions about whether long-term consumption of folate and folic acid may increase the risk of developing certain cancers in some people.
The debate is far from benign. Food manufacturers are required to add folic acid to enriched flour and grain products under federal regulations that came into force in 1998. The premise behind fortification, which was also mandated in the United States, is to ensure that women receive adequate levels of folate in order to reduce the risk of birth defects in their offspring.
A decade later, however, new research and scientific studies have found evidence that increased consumption of folic acid may help trigger the onset of colon and other types of cancer.
Folic acid is the synthetic form of folate, which is a B vitamin that occurs naturally in leafy greens and other fruits and vegetables. It has been shown to significantly reduce the chance of neural tube defects, such as spina bifida, and helps produce and maintain healthy cells and is involved in numerous biological functions.
The new Canadian research, presented yesterday at the annual meeting of the American Association for Cancer Research in Denver, found that folic acid consumption by the mother has effects on her offspring.
The research is part of a burgeoning field of science known as epigenetics, which studies how gene activities are changed or influenced by diet, lifestyle and other environmental factors. Certain genes can become activated or rendered dormant depending on these factors.
In some cases, genes that protect the body against certain types of cancer can be shut off, while genes that promote tumour formation can be turned on. Changes to genes can also trigger mutations, which explains why epigenetics has been gaining so much attention in the scientific community for its potential ability to help explain the mystery of disease risk.
In the new study, led by Karen Sie, a research scientist in the University of Toronto's faculty of medicine, researchers gave two groups of laboratory rats folic acid supplementation. One group received the equivalent of the daily recommended intake for humans, 0.4 milligrams, and the other group received a higher dose, equal to 1 milligram in humans, which is the maximum recommended daily intake for women during pregnancy.
They found that offspring of rats that received the higher dose experienced a much higher degree of changes to genes in the colon and liver shortly after birth. But as the rats aged, there was a significant drop in the changes to genes.
The researchers don't yet know which specific gene functions were changed. It could be that the high degree of changes noted shortly after birth could silence genes designed to suppress tumours. But the changes could also activate genes that help protect against cancer.
Regardless, the discovery that folic acid can turn genes on or off could help in the quest to determine whether the supplement does contribute to increased risk of cancer in some people.
"The concern is with the high dose that people are getting nowadays," Ms. Sie said.
Despite the new findings, there are still strong defenders of folic acid fortification.
"We know ... folic acid is needed to prevent neural tube defects," said Gideon Koren, director of the Motherisk program at Toronto's Hospital for Sick Children. "As we talk now, 40 per cent of women in Canada do not have enough folic acid to protect the baby from spina bifida and other malformations."
Dr. Koren said Canada's fortification program is one of the key elements needed to reduce the incidence of neural tube defects, and that considering changes because of results from studies that primarily involve rats could be dangerous.
However, others say it's becoming harder to ignore the growing debate about folic acid. Despite its clear benefits when taken by pregnant women, the move to fortify food with folic acid means a major portion of the population is consuming a higher level of the supplement than they would otherwise.
Now, concern is growing that parts of the population that may be susceptible to colon cancer and other diseases could be put at greater risk due to their inadvertent exposure to folic acid.
"It's a real dilemma," said Joel Mason, associate professor of medicine and nutrition and director of the Vitamins and Carcinogenesis laboratory at Tufts University in Boston, who specializes in folic acid and folate.
And there are no simple solutions. Putting an end to fortification could put more women at risk of having babies with neural tube defects. But keeping folic acid supplements in the food supply could put certain people at a higher risk of disease.
A significant amount of research is currently being conducted to answer these questions, including studies looking at whether North American folic acid fortification led to changes in the population rates of certain types of cancer.
Dr. Mason said that despite any fears over safety, the research is too preliminary to warrant changes to fortification programs. But government regulators should be paying close attention as new research emerges, he said.