Supplement folic acid, it is well known that supplementing with FA can significantly reduce the risk of birth defects.
Research Background
To reduce the incidence of neural tube defects (NTDs) and congenital heart defects (CHDs) in newborns, more than 80 countries have implemented mandatory folic acid food fortification programs.
Some people are exposed to folic acid concentrations that are higher than the recommended daily allowance (RDA) of 0.4 mg due to the increased intake of folic acid from various dietary supplements. These people include women with previous NTD syndrome pregnancies who are planning to become pregnant again and men with fertility issues who are receiving high-dose FA (12.5 times the RDA) for improving sperm count.
There isn't enough data, though, to say whether consuming too many FAs might endanger people.
Cell discovery_Excess folic acid intake increases DNA de novo point mutations
Recently, a research team led by Professor Wang Hongyan of the Obstetrics and Gynecology Hospital of Fudan University and Professor Richard H. Finnell of Baylor College of Medicine in the United States has published an important research paper in the renowned journal "Cell Research."
For the first time worldwide, they used whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS) technologies to explore the effects of different levels of folic acid intake on DNA mutations in the offspring of mice.
The research found that compared with normal levels of intake, inadequate parental folic acid intake doubled the number of new heterozygous single nucleotide variants (DNSNVs) in embryos, while excessive parental intake increased the number of new heterozygous single nucleotide variants (DNSNVs) in embryos by 80%.
In other words, supplement folic acid should be controlled within a specific range, as inadequate or excessive intake can have adverse effects on the health of offspring.
Experiment Details
Researchers used C57BL/6 J mice as the subject of their study, and these mice were given one of three different folic acid intakes: low dose (0.3mg/kg), control dose (3mg/kg), and high dose (30mg/kg). The controlled dose is equivalent to one-quarter to one-half of the daily recommended amount for humans (0.4mg).
After being fed for four months, the mice on low and high folic acid diets, as well as the control group, were mated with mice from the control group. This means that in all pairings (77 pairs), at least one of the mice was on a normal diet. Subsequently, the researchers collected DNA from all parents and from fully-formed embryos at 12.5 days (E12.5) and conducted whole-genome sequencing.
The research team found that compared to the control group, the DNA mutation rate in the low-dose group of mice increased by 2 times, and in the high-dose group it increased by 1.8 times. Additionally, in the high-dose group, the methylation level of DNA repair genes was significantly increased. Methylation inhibits gene expression, suggesting that excessive folic acid supplementation may affect DNA mutation rates by reducing the expression of DNA repair genes and impairing DNA repair activity.
The research team stated that these experimental data indicate "The Blonde Girl Effect" for Supplement folic acid - moderation is key, too much or too little is not good. This also suggests that its supplementation should be limited to an ideal range.
Cao, X., Xu, J., Lin, Y.L. et al. Excess folic acid intake increases DNA de novo point mutations. Cell Discov 9, 22 (2023).