A study has reported that daughters of rats who were given folic acid supplements before conception, during pregnancy, and while nursing had twice the breast cancer rate as similar daughter rats whose mothers were not given folic acid. The daughter rats of folic acid-supplemented mothers also had more mammary tumors and developed them at a faster rate. Prenatal and early life exposure to folic acid has increased significantly in North America as a result of fortification of foods, widespread folic acid supplement use, and conception-related supplementation. Folate is a water-soluble B vitamin found in a variety of foods, whereas folic acid is a synthetic form of the vitamin found in supplements and fortified foods. Women are currently advised to take folic acid supplements before becoming pregnant and during pregnancy to prevent neural tube birth defects such as spina bifida. The Canadian and U.S. governments require food manufacturers to add folic acid to white flour, enriched pasta, and cornmeal to ensure that women receive enough of this B vitamin.

In the study, female rats were fed either a control diet or the control diet plus folic acid before mating and during pregnancy and nursing. The folic acid supplementation was designed to be approximately equivalent to what pregnant women typically take plus what they consume through mandatory food fortification. Female pups from both maternal diet groups were randomly assigned to the control or folic acid supplemented diet upon weaning. Mammary tumors were induced with a carcinogen in all of the daughters at puberty.

Both folic acid supplementation of the mothers and postweaning folic acid supplementation of the daughters were found to double the rate of mammary tumors in the offspring. In other words, both the rats whose mothers were given folic acid and the offspring who were given folic acid had twice the rates of mammary tumors compared to the unsupplemented control groups. Maternal folic acid supplementation also was found to significantly accelerate the appearance of mammary tumors and increase their number in daughter rats. Folate has a role in making and replicating DNA. Maternal, but not postweaning, folic acid supplementation was observed to significantly reduce global DNA methylation (how genes are turned on and off). Widespread loss of genomic DNA methylation is an early and regular step in cancer development, including breast cancer. The authors conclude that high prenatal and postweaning dietary exposure to folic acid may increase the risk of mammary tumors in rat offspring. This tumor-promoting effect may be mediated in part by altered DNA methylation and DNA methyltransferase activity.

Implications of the study

Currently, it is recommended that all women of childbearing age take 0.4mg folic acid per day or to obtain this amount from fortified foods. This is because folic acid reduces the risk of neural tube defects such as spina bifida and anencephaly when taken before conception and during early pregnancy. As noted above, many grain products such as enriched flour, rice, pasta, bread and cereals contain added folic acid in the U.S. as a result of mandatory folic acid fortification regulations.

While the results of this study need to be replicated, they are alarming and supported by a fairly convincing explanation of the mechanism of action. Therefore, we find them worth paying attention to until further evidence is published. While adequate maternal folate levels clearly are necessary for preventing neural tube defects in children, these do not necessarily have to be achieved through folic acid supplementation. We suggest that women who plan to have children get their folate levels checked well before becoming pregnant. This will give them the opportunity to increase their circulating folate levels through their diets (see the list of foods below) and by eliminating alcohol consumption, if necessary. Women with folate levels in the high end of the normal range do not need folic acid supplementation during pregnancy. Those that are not able to achieve this level may need to take folic acid supplements.

Furthermore, while we encourage all women to consume foods rich in folate, we do not see a reason for survivors of breast cancer or women at high risk for breast cancer to take folic acid supplements. It has not been convincingly demonstrated that such supplements reduce the risk of breast cancer in U.S. women. Moreover, it is possible that folic acid supplements might promote the progression of early precursor lesions to breast cancer, as well as the growth of existing, undiagnosed tumors.

Good dietary sources of folate

The following foods are good sources of folate, as well as being on our recommended food list for breast cancer in general:

Broccoli
Beans, dry
Bell peppers
Cabbage
Cauliflower
Celery
Collard greens
Lettuce, romaine
Liver, chicken or turkey
Mustard greens
Parsley
Squash
Note that both green and black tea reduce intestinal absorption of folate and should not be consumed simultaneously with high-folate foods by those wishing to increase their circulating folate levels.

Please see our article on how to protect our daughters from future breast cancer during the prenatal period for more information on how to reduce breast cancer risk in girls.