Folic acid supplementation provided in utero and during lactation reduces the number of terminal end buds of the developing mammary glands in the offspring

Folate may prevent or promote cancer development and progression depending on the timing of intervention. Intrauterine exposure to folic acid has drastically increased in North America due to mandatory fortification and supplemental use of folic acid, which may influence the risk of breast cancer in the offspring. We investigated the effect of maternal folic acid supplementation, equivalent to the likely average post-fortification folate intake of a North American woman taking multivitamins containing folic acid, on terminal end buds, which reliably predict mammary tumor risk at adulthood in rodents. Female rats were placed on a control or supplemental diet for 3 weeks prior to mating and throughout pregnancy and lactation. Female pups were placed on the control diet at weaning until 50 days of age. The pups from the folic acid supplemented dams had a significantly lower number of terminal end buds than the pups from the dams fed the control diet (p = 0.014). Our data suggest for the first time that folic acid supplementation provided in utero and during lactation may lower mammary tumor risk in the offspring.