Folic Acid Deficiency May Cause Multigenerational Health Problems

CAMBRIDGE, EnglandFolic acid deficiency can cause severe health problems in offspring, including spina bifida, heart defects and placental abnormalities, according to a study published in the journal Cell.

Researchers at the University of Cambridge identified a mutation in a gene necessary for the metabolism of folic acid not only impacts the immediate offspring, but can also have detrimental health effects on the next several generations.

"Our research shows that disease in general can be inherited through epigenetic means rather than genetic means, which has huge implications for human health. Environmental factors that influence epigenetic patternse.g., diet, epigenetic disruptors in the environment, such as chemicals, etc.may also have long term, multigenerational effects."

As the detrimental effects of folic acid deficiency on development are well known, many countries, including Canada and the United States, have implemented folate fortification programs that require folic acid to be added to cereal products. Until now, very little was known about how folic acid deficiency caused the diverse range of health problems in offspring.

"Fortification programs have reduced the risk of health effects but not eliminated them completely," said Dr. Erica Watson from the Centre for Trophoblast Research at the University of Cambridge, who led the study. "Based on our research, we now believe that it may take more than one generation to eliminate the health problems caused by folate deficiency."

For the study, the scientists used mice in which a gene called Mtrr was specifically mutated. The gene is key to the normal progression of the folic acid cycle and, when mutated, it results in abnormal folic acid metabolism causing similar effects to dietary folic acid deficiency. The researchers found that when either the maternal grandmother or the maternal grandfather had this Mtrr mutation, their genetically normal grandchildren were at risk of a wide spectrum of developmental abnormalities. These developmental abnormalities were also seen in the fourth and fifth generations of mice.

Through another experiment which involved transferring the embryo from the third generation into a normal healthy female mouse, they discovered that these developmental abnormalities were not passed down genetically. Instead, the serious defects were the result of epigenetic changes which had been inherited.