The Bad News About Folate Deficiency: The Damage It Causes Can’t Be Undone

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A new study has revealed that a lack in folate causes problems with cell division and DNA replication. What’s worse, the consequences are much more serious than previously thought.

Folate is a vitamin essential to human health. However, because the body can’t store it, it has to be obtained through folate-rich foods or by taking folic acid (man-made folate) supplements. It’s difficult finding a pregnant woman today who doesn’t know folate’s importance in preventing birth defects. A fact perhaps less widely known is that this vitamin (also known as vitamin B9) may also protect against anaemia, infertility, many cancers, psychological disorders and age-associated dementia. However, it’s still unclear to scientists how precisely a deficiency in folate could cause such a wide range of illnesses.

A recent study published in the journal ‘Proceedings of the National Academy of Sciences’ has shed a bit of light on the matter. Supported in part by the EU-funded CHROMAVISION project findings show that folate deficiency can cause problems related to cell division and DNA replication. In fact according to the study’s authors the chromosomal abnormalities created by this deficiency are far more detrimental than scientists previously believed.

“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 study author Ying Liu an associate professor from the Department of Cellular and Molecular Medicine of the Center for Chromosome Stability at project partner University of Copenhagen in an article posted on the research news website ‘Futurity’.

The researchers analysed the genetic locus called FRAXA, which contains an extensive repeat sequence of the chemical pattern cytosine-guanine-guanine (CGG). They showed that folate deficiency triggers faulty chromosomal segregation at this locus. Additionally, they found that long-term folate deprivation causes the entire chromosome X to become unstable.

“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.

There are several loci in the human genome where the CGG pattern is extensively repeated. According to the study’s authors, further research focusing on these regions is needed to see whether folate deficiency could cause chromosome instability in them and consequently disease over time.

CHROMAVISION (Super-resolution visualisation and manipulation of metaphase chromosomes) will be ending in May 2019. The project’s contribution to better imaging and a clearer understanding of chromosomal mechanisms is helping scientists figure out the causes of diseases and discover new drugs.

For more information, please see: CHROMAVISION project website