Excess oral folic acid does not elevate formaldehyde genotoxicity in humans
Moonshot Award
Proposal Development
Abstract
Folic acid is consumed by millions and frequently prescribed at high doses to patients with blood disorders or cancer. However, excess folic acid supplementation has been associated with increased DNA damage, raising concerns over the safety of high-dose intake. One potential mechanism is that folate metabolites are chemically unstable and can decompose to release formaldehyde, a genotoxin and human carcinogen. Whether excess folic acid increases formaldehyde-driven DNA damage in the body, especially in these vulnerable patients, had not been tested.
To this end, we conducted a clinical study with Cayuga Cancer Center to measure the level of formaldehyde-DNA adducts, a stable biomarker of formaldehyde in blood cells from cancer patients prescribed high dose folic acid compared to patients not taking folic acid. Reassuringly, formaldehyde-DNA adduct levels were not elevated in patients taking folic acid despite elevated folate levels in their blood. This correlates with similar experiments performed using animal models.
Overall, we provide evidence that increased oral folic acid intake does not elevate formaldehyde-DNA damage, providing added safety profile to this common nutrient supplement, and shows how partnership with a local cancer center can bring clinical research within reach of the Ithaca community.
