Folic acid is a man-made version of vitamin B9. It is added to bread and cereal. Doctors also give it in large amounts to cancer patients and people with blood disorders. A new study says this does not raise harmful formaldehyde in the body. This is good news for anyone who depends on folic acid supplements.
Folate is the natural form of this vitamin. Our bodies cannot make it on their own. We get it from food like beans, spinach, and asparagus. Folic acid is the lab-made version. It is more stable and easier to store. That is why it gets added to packaged foods. Doctors also prescribe it during pregnancy, for sickle cell anemia, and during chemotherapy.
Once inside the body, folic acid turns into an active form called tetrahydrofolate. Earlier lab experiments showed something concerning. In test tubes and cell cultures, tetrahydrofolate can break down. When it does, it releases formaldehyde. Formaldehyde is a known carcinogen. It can also damage DNA. Scientists wondered if this same breakdown happens inside living bodies, not just in a lab dish.
A team at Cornell University set out to answer that question. They worked with the Cayuga Cancer Center on the project. Their findings appeared in the journal EMBO Molecular Medicine. The results were reassuring. In cell cultures, formaldehyde and DNA damage did increase, as expected. But in live mice and in cancer patients, nothing similar occurred. No extra formaldehyde and no extra DNA damage showed up.
Dr. Meng Wang led the research. She works in Cornell’s Division of Nutritional Sciences. Wang said the findings offer real comfort. This matters most for people who need very high doses of folic acid. She pointed to patients with Fanconi anemia as a key example. This is a rare condition linked to cancer. People with it cannot repair DNA damage from toxins like formaldehyde very well. So confirming that folic acid is safe for them carries extra weight.
To test the theory carefully, researchers used special mice. These mice were bred without a key enzyme. That enzyme normally breaks down formaldehyde. The mice also lacked the ability to fix formaldehyde-related DNA damage. This made them extremely sensitive. Even a tiny rise in formaldehyde would be easy to detect in these animals.
The mice ate one of two diets for eight weeks. One group got a normal amount of folate. The other group received ten times the usual amount, all as folic acid. Researchers then used a highly sensitive method called mass spectrometry. This let them search for formaldehyde attached to DNA. These attachments are called DNA adducts. They act as reliable markers of formaldehyde exposure.
The results were clear. Mice on the high-folic-acid diet did have more tetrahydrofolate in their livers, as expected. But their formaldehyde levels stayed normal. Their DNA and tissue showed no extra damage either.
Next, the team wanted to know if humans would respond the same way. They partnered with Dr. Anthony Mato, an oncologist at Cayuga Cancer Center. Together, they studied blood samples from real cancer patients. Nine patients were taking high doses of folic acid. Fifteen others were not. Folate levels rose in the group taking supplements, just as expected. But formaldehyde-DNA adducts did not increase in either group.
Wang said testing real patients was an essential step. Mouse data alone would not have been enough. The human results matched what her team saw in mice. This strengthens confidence in the overall conclusion.
The study’s first author is Chris Mellor, a postdoctoral researcher in Wang’s lab. Other contributors include Martha Field, John Blenis, and Guillermo Burgos-Barragan. Funding came from several sources. These include the National Institutes of Health, the St. Baldrick’s Foundation, the American Association for Cancer Research, the Fanconi Cancer Foundation, and Cornell’s CALS Moonshot Award.
