High-dose folic acid appears safe from formaldehyde toxicity

Folic acid – an essential vitamin added to flour and cereals and prescribed at high doses for cancer patients and people with blood disorders – does not elevate toxic formaldehyde in the body, according to a new Cornell University study on mice and human cancer patients who consumed high doses. 

Previous studies have shown that in a test tube and in cell culture, tetrahydrofolate naturally decomposes to release formaldehyde, a carcinogen and genotoxin known to damage DNA. These results raised the question of whether the same thing happens in the body, which has direct health implications for the millions of people who take folic acid. 

This was addressed by a new study, published in the journal EMBO Molecular Medicine and conducted in partnership with the Cayuga Cancer Center, showing that while tetrahydrofolate does indeed increase formaldehyde and DNA damage in cell culture, no evidence of this toxin or DNA damage was found in mice or human cancer patients who received high doses of folic acid. 

"Our study provides reassurance, particularly for patients who need higher levels of folic acid supplementation, that formaldehyde is not increased as a toxic side effect," said Dr. Meng Wang, assistant professor in the Division of Nutritional Sciences, and the paper's senior author. "This is especially important for cancer patients with Fanconi anemia, a rare cancer syndrome caused by deficiency in a DNA repair pathway against toxins like formaldehyde." 

Mammals cannot make folate (vitamin B9), an essential nutrient needed to support normal cell growth such as building DNA. While the nutrient is naturally rich in foods including beans, spinach and asparagus, folic acid – a stable and synthetic form of folate – is often recommended as a supplement in higher doses. Folic acid is widely added to breads and cereals, prescribed during pregnancy to prevent birth defects, to people with blood disorders such as sickle cell anemia and to cancer patients during chemotherapy treatment. 

To test their animal findings in humans, Wang's team collaborated with study co-author Dr. Anthony Mato, an oncologist at the Cayuga Cancer Center at Cayuga Health, to examine blood samples from local cancer patients prescribed high dose folic acid supplementation.

"It was critical to obtain human data to confirm whether our results also translated into the human population," Wang said.

In the blood from nine patients taking high dose folic acid compared to 15 patients not taking folic acid, the levels of folate increased but formaldehyde-DNA adducts did not.