Medical professionals have known for a long time that deficiencies in folic acid can cause severe health problems for offspring, such as spina bifida, heart defects, and placental abnormalities. What they did not know is that folic acid deficiencies can cause defects in offspring for several future generations. A new study, published in the journal Cell, sheds new light on the role folic acid plays on a molecular level during fetal development.

The Nature of Folic Acid
Folic acid, also known as folate, is a form of vitamin B found naturally in many foods or as a supplement. Low intake during maternity is associated with birth defects of the brain or spine known as neural tube defects, low infant birth weight, preterm delivery, and fetal growth retardation. Many countries, including the United States and Canada, have fortification programs that require food makers to add folate to cereal products. This program has worked well to reduce the incidence of folic acid deficiencies; folate deficiencies are now rare in the U.S. and Canada.

Some people, however, are still at risk for developing folic acid deficiencies – especially pregnant women. During pregnancy, folic acid is integral in the synthesis of nucleic acid, which allows organisms to pass genetic information from one generation to the next. To ensure women enough folic acid to pass genetic information onto children, the National Institutes of Health’s Office Dietary Supplements suggests 400 mcg per day for non-pregnant women to 600 mcg each day during pregnancy.

"Fortification programmes 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 and leader of 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."

The research team used mice in which the Mtrr gene called was specifically mutated to interfere with folate metabolism to cause a folic acid deficiency. The scientists used mice because the rodents metabolize folate similarly to humans and folic acid deficiencies cause the same problems in mice offspring as they do in human babies. This study helped researchers to see how folic acid deficiencies cause problems in not only immediate offspring but in subsequent generations of mice as well.


  • Nisha Padmanabhan, et al. "Mutation in Folate Metabolism Causes Epigenetic Instability and Transgenerational Effects on Development." Cell. Volume 155, Issue 1, 26 September 2013. Retrieved 8 Oct 2013.
  • "Folate." Office of Dietary Supplements. National Institutes of Health. 14 Dec 2013. Web. 8 Oct 2013.