The study, published in PloS One, investigated whether folic acid supplementation are linked to an increased risk for the progression of established mammary tumours using a rat model after previous research suggested a link between high intakes of the B vitamin and breast cancer risk.
"Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown," explained the research team - led by Professor Young-In Kim of St. Michael's Hospital and the University of Toronto, Canada.
"This is a critically important issue because breast cancer patients and survivors ... are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis," the team noted.
Kim and his team compared cancer outcomes in rats randomised to receive between 2.5 and 5 times the daily requirement of folic acid or a control diet - finding that the high level of folic acid 'significantly' promoted growth in both existing pre-cancerous or cancerous cells.
"Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumours and was associated with significantly higher sentinel mammary tumour weight and volume compared with the control diet," revealed the team. "Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumours."
Study details
The team investigated whether folic acid supplementation was associated with the promotion and progression of established mammary tumours. in female Sprague-Dawley rats.
The rats were placed on a control diet before mammary tumours were initiated using 7,12-dimethylbenza[a]anthracene at puberty.
"When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks," explained the team.
Although no clear dose-response relationship was observed, folic acid supplementation was found to significantly promote the progression of the sentinel mammary tumours and was associated with significantly higher sentinel mammary tumour weight and volume compared with the control diet.
Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumours, said the team.
"The most significant and consistent mammary tumour-promoting effect was observed with the 2.5x supplemental level of folic acid," they revealed. "Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2."
"The potential tumour-promoting effect of folic acid supplementation in breast cancer patients and survivors needs further clarification," they said.
Source: PLoS One
Published online ahead of print, doi: 10.1371/journal.pone.0084635
"Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model"
Authors: Shaidah Deghan Manshadi, Lisa Ishiguro, et al