Folate deficiency has been associated with mental illness, age-related dementia, infertility and fetal deformation of the brain and spinal cord (neural tube defects).
But so far, researchers have been unable to determine causality; that is, whether folate deficiency directly causes the disorders or whether the disorders are caused by a secondary effect of folate deficiency.
In a new Danish study, researchers from the University of Copenhagen show that folate deficiency can directly and severely affect one of the most important processes in the body: cell division. In fact, a deficiency creates far more problems with chromosomal abnormalities than researchers had previously believed, and once a person lacks folate, the resulting damage cannot be reversed.
The researchers therefore encourage people to be more aware of the level of folate in the blood. A blood sample can determine the level of folate in the blood.
Folate is a type of B vitamin found in foods such as legumes, broccoli, spinach, mushrooms, shellfish, bananas, oranges and melon. The Danish Health Authority recommends that pregnant women and women trying to become pregnant take a daily supplement of folic acid.
But everyone, not just pregnant and soon to be pregnant women, should focus on this vitamin, says study author Associate Professor Ying Liu from the Center for Chromosome Stability at the Department of Cellular and Molecular Medicine, UCPH.
“The problem with folate deficiency is that it affects chromosome maintenance, and once a cell has lost a chromosome or part of it, it can never be fixed. That is, once cell division has gone wrong, you cannot fix it subsequently by consuming a lot of folic acid. Once the damage is done, it is irreversible,” Liu said.
“Therefore, we need a guide telling us what the level of folate in the blood in the population in general should be. Once we have that knowledge, we can determine whether a person needs folic acid supplements to make sure the level in the blood is high enough for the cells to reproduce the DNA successfully.”
For the study, the researchers looked at lymphocytes, a type of white blood cell, from men. However, the results would also apply to women, said Liu.
The team analyzed the part of the genome called FRAXA, which contains an extensive genetic code known as the CGG sequence. Here they saw that folate deficiency caused abnormalities in connection with cell division, especially in cells with an abnormally long CGG sequence.
The researchers also saw how the entire X chromosome became unstable in cases of long-term folate deficiency.
“In the study, we demonstrate that folate deficiency leads to both higher levels of and more harmful chromosome abnormalities than previously known. This causes the daughter cells to inherit the incorrect amount of DNA following cell division or, in some cases, to even lose an entire chromosome. This could explain why folate deficiency is associated with diseases like infertility, mental health disorders and cancer,” Liu said.
Other parts of the genome also contain extensive CGG sequences. The researchers assume that these regions will also be affected by folate deficiency. Next, they hope to map all the areas of the human genome that may be affected by folate deficiency.
The findings are published in the scientific journal PNAS.