Antioxidants are purported as a crucial part of optimal health and frequently come up in discussions about disease prevention, but new research published in Science Translational Medicine suggests that the presence of these substances in type 2 diabetes medications may fuel the spread of cancer. “The administration of drugs with antioxidant activity in cancer patients, such as diabetic patients with cancer, should be carefully evaluated,” study author Shicang Yu told Medical Daily.

Antioxidants are molecules that prevent or delay some types of cell damage by helping to neutralize the harmful molecules, or free radicals, that attack our cells and DNA to cause different types of diseases. They occur naturally in fruits and vegetables, but can also be man-made, and are commonly used to treat patients with diabetes, a disease driven by oxidative stress and thought to increase cancer risk. Although their connection with cancer is poorly understood, various studies have shown antioxidants to worsen cancer outcomes despite their protective properties.

“Accumulating epidemiological evidence suggests that diabetes increases the risk of multiple cancers, including colon, liver, and breast cancers,” researchers wrote. “Therefore, the increased prevalence of diabetes suggests that the incidence of individuals with both diabetes and cancer is also rising.”

For the recent study, researchers explored the effects of two common classes of antidiabetic medications with antioxidant properties on mice with colon and liver cancer. While the drugs did not raise the risk of developing cancer, they did increase the likelihood that existing cancers would metastasize. It appears that the antioxidants in the antidiabetic drugs used their protective properties to the cancer cells’ benefit. Researchers found that the drugs seemed to protect cancer cells from oxidative stress, boosting their ability to migrate and invade. To further understand this relationship, researchers conducted cell experiments, which revealed that the antidiabetic drugs activated NRF2 signaling pathway, a protein that regulates the expression of antioxidant proteins.

This activation triggered the expression of metastasis-promoting proteins. Based on these findings, researchers said that deleting or blocking NRF2 could reduce cancer cell migration. In addition, researchers also analyzed 176 liver tumor samples from humans and found that NRF2 expression correlated with tumor metastasis, offering a potential therapeutic target to prevent tumor growth.

“Our findings indicate that antioxidants that activate NRF2 signaling should be administered with caution in cancer patients,” researchers concluded.

The study builds on past research that has linked antioxidants to accelerated cancer growth.

The presence of these compounds in antidiabetic drugs is bad news for diabetic patients since cancer is a common comorbidity of this group. What’s more, according to the study, the number of diabetic patients who also have cancer is growing.

Researchers say more studies are needed to evaluate the safety of antioxidant-containing medications for diabetic patients with cancer and want to confirm their findings in humans before any definitive clinical recommendations could be made.

Source: Wang H, Liu X, Long M. NRF2 activation by antioxidant antidiabetic agents accelerates tumor metastasis. Science Translational Medicine. 2016.