Once you lack folate, the damage can’t be fixed

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Folate deficiency creates more problems in connection with cell division and DNA replication than previously thought, a study shows.

Once a person lacks folate, the resulting damage is irreversible. The researchers therefore encourage people to be more aware of the level of folate in the blood.

Folate is a type of vitamin B found in, for example, broccoli, spinach, peas, mushrooms, shellfish, and fruit such as bananas and melon. The Danish Health Authority recommends that pregnant women and women trying to get 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 the last author of the study, associate professor Ying Liu from the Center for Chromosome Stability at the department of cellular and molecular medicine at the University of Copenhagen.

“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,” says Liu.

“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.”

A blood sample can determine the level of folate in the blood. Researchers have known for many years that folate deficiency is associated with mental illness, age-related dementia, and deformation of the brain and spinal cord of fetuses, also known as neural tube defects. But they have not been able to establish the causality—that is, whether folate deficiency directly causes the disorders or the disorders result from the secondary effect of folate deficiency.

To answer this question, the researchers studied lymphocytes, which are a type of white blood cell, from men. However, the results would also apply to women, Liu says.

The researchers analyzed the part of the genome called FRAXA, which contains an extensive so-called CGG sequence, a genetic code. Here they saw that folate deficiency caused abnormalities in connection with cell division, mitosis, especially in cells with an abnormally long CGG sequence. Among other things, it caused faulty segregation of chromosomes. The researchers also saw how the entire X chromosome became unstable in cases of long exposure to 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 explains.

Other parts of the genome also contain extensive CGG sequences. The researchers assume that folate deficiency will also affect those regions. As a next step, they aim to map all the areas of the human genome that folate deficiency may affect.

The research appears in PNAS. Funding came from the Nordea Foundation, the US National Institute of Health, the Danish National Research Foundation, and the European Union Horizon 2020 program.

Source: University of Copenhagen