“Overall, maternal folic acid supplementation before and during pregnancy seems to confer protection against the risk of childhood leukaemia in the offspring,” concluded the review which appears in Genes & Nutrition.
The importance of maternal folic acid for preventing neural tube defects (NTDs) in pregnancy is well established. The review, conducted by researchers from Palermo University and Brunel University, London, examines recent studies involving folate’s effect on DNA methylation, cancer progression and prevention. It also analyses observational studies linking folic acid intake with incidence of childhood leukaemia.
Previous work has identified folate’s role for DNA methylation, synthesis and repair within cells.
This review, led by Catia Cantarella, observed “Folic acid deficiency is capable of interfering with these processes, which are extremely important during foetal development and, if altered, are capable of promoting carcinogenesis and the development of other diseases. In particular, DNA damage due to lack of folates can lead to the formation of chromosomal abnormalities, which are considered a hallmark in cancer and leukaemia.”
The review also noted that DNA damage resulting from low folate status occurred in both the cell nucleus and mitochondria. Extensive DNA damage results in a high frequency of mutations to the genome, known as genomic instability, a characteristic of cancer progression.
Although not unanimous, most studies included in the review found that both acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) risk decreased with folic acid intake. Some studies also suggested chemoprotective benefits of taking multivitamins together with folic acid.
Folic acid intake prior to conception, as well as during pregnancy, was considered important by the review.
“Leukaemogenesis appears to be a result of genetic and environmental factors, occurring prior and during pregnancy,” the team noted.
Data from the majority of observational studies in the review supported this finding.
The studies were nevertheless purely observational and therefore no causality can be confirmed. Additionally, ethical considerations preclude using a placebo group in any RCT involving folic acid intake during pregnancy.
UK NHS and US NIH recommendations for daily folic acid intake during pregnancy are 400 ug and 600 ug respectively. These levels are aimed at minimising NTDs and risk of foetal malformations. However, the review was unable to provide guidance on dosage to minimise leukaemia risk.
“The exact optimal dosage is still unclear, considering that excessive intake of folic acid might have serious drawbacks, including the nourishment of pre-existing cancers or pre-cancerous conditions.”
Source: Genes & Nutrition
Volume 12: 14, doi: 10.1186/s12263-017-0560-8
“Folate deficiency as predisposing factor for childhood leukaemia: a review of the literature”
Authors: Cantarella CD, et al