Not just for pregnant women: Folate deficiencies can cause irreversible DNA damage across demographics, study warns

18 Dec 2018 --- Folate deficiency creates more problems in connection with DNA replication than previously assumed, researchers from the University of Copenhagen have reported. The findings show that once a person is folate deficient, the “chromosomal abnormalities” and damage caused cannot be reversed. The research widens the scope of people who should be aware of their folate consumption from pregnant women to all demographics, especially in regions where the supply of folate in the food supply may be low.

The effects observed came to the fore on cells who were deficient in folate for only three days, although the problems became more severe with time, Ying Liu, last author of the study and Associate Professor at the Center for Chromosome Stability at the Department of Cellular and Molecular Medicine, UCPH tells NutritionInsight.

“The problem with folate deficiency is that it affects chromosome maintenance. Once a cell has lost a chromosome or part of it, it can never be fixed. You cannot fix it subsequently by consuming a lot of folic acid. Once the damage is done, it is irreversible,” says Liu.

Folate is a type of vitamin B found in a range of foods such as broccoli, spinach, peas, mushrooms, shellfish and bananas. The Danish Health Authority recommends that pregnant women and women trying to get pregnant should take a daily supplement of folic acid. However, as a result of the findings, the researchers are calling for everyone to pay attention to this vitamin. 

Inside the research
The study sought to identify the unknown causality between folate deficiency and mental illness, age-related dementia and neural tube defects (NTD). The key question to address was whether folate deficiency directly causes the disorders or if the disorders are caused by the secondary effect of folate deficiency.

To answer this question, the researchers studied lymphocytes; a type of white blood cell from men. However, the results would also apply to women, Liu points out.The Danish Health Authority recommends that pregnant women and women trying to get pregnant should take a daily supplement of folic acid.

The researchers analyzed the part or area 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, 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.

“We demonstrated 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.

Therefore, it is important to have a guide that can share what the level of folate should be in the blood for the general population, Liu explains.

“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,” she adds.

Regarding future research, Liu notes that other parts of the genome also contain extensive CGG sequences, which the team assumes will also be affected by folate deficiency. In a future study, they plan to map all the areas of the human genome that may be affected.

Furthermore, Liu notes that some governments are reluctant to use folate fortification, necessitating more data to guide policy makers to make the right decision.

Folate deficiency at the time of conception can have a damaging effect on fetal development, increasing the likelihood of having a premature or low-birth-weight baby and increasing chances of NTD at birth, for example.

This means the consumption of folic acid by pregnant women and women trying to get pregnant is well documented and has received quite some attention. 

The recommended daily amount of folate for adults is 400 micrograms (mcg). Adult women who are planning pregnancy or could become pregnant should be advised to get 400 to 800 mcg of folic acid a day.

In October, the UK proposed to fortify flour with folic acid, a move that was called “long overdue, but welcome” by UK nutritionists. Despite countries such as the US, Canada and Australia having mandatory folic acid fortification policies, the UK had not followed suit until then. 

The UK instead took a voluntary approach, including marketing campaigns attempting to highlight the necessity of folic acid supplementation in reproductive ready women. However, recent figures showed that the approach did not bear the desired results.

The latest National Diet and Nutrition Survey noted that 91 percent of women of childbearing age have a red blood cell folate level below the level (748nmol/L) estimated to lower risk of NTD. 

The importance of folate has been hugely publicized regarding the health of babies, and the UK government’s move to implement a fortification strategy is arguably a strong step toward ensuring the health of a new generation of babies. However, this new study sheds light on the importance of the vitamin for the general population, which may reignite the need for fortification or supplementation among other groups.

By Laxmi Haigh