Excess antioxidants, like Vitamin E—long thought to be cancer-preventers—can actually help lung cancer cells spread throughout the body, according to two new studies jointly published in the journal Cell this morning.
You wouldn’t be blamed for thinking that antioxidants—found in vitamin E, vitamin C, and beta-carotene—are anti-cancer compounds. They are, after all, common elements of the all-powerful “superfoods”: things like blueberries, red grapes, dark leafy greens, and dark chocolate. They’re healthy, end of story. Right?READ MORE
When it comes to the spread of lung cancer, this may not be entirely true. This finding comes from two studies—one led by researchers at the NYU School of Medicine and the other led by researchers at the Karolinska Institutet in Sweden. The NYU study focused on the biological link between antioxidants and cell metastasis, and the Karolinska Institut focused on how ingesting excess antioxidants (like vitamin E supplements) can that can actually help lung cancer cells spread to other parts of the body. Together, the two studies showed not only that antioxidants can have this effect, but also why it happens, biologically speaking.
The reason for this phenomenon is pretty complicated, but Dr. Michele Pagano, Chair of the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health and the senior author on the NYU study, explained to us that it has to do with gene mutations, proteins, and pathways in the body.
To understand the process, it’s important to first understand what antioxidants actually are, and how they work.
Antioxidants Neutralize Cell-Damaging Oxidation
Antioxidants, true to their name, are compounds that counteract oxidation (“anti” oxidizers). Oxidation can happen in a lot of things (rusting metal is an example of oxidation, and so is an apple turning brown), but in the context of a human body, it’s a gradual cell-damaging process that happens when unstable molecules called “free radicals” harm cell DNA. The body naturally makes free radicals when it breaks down nutrients into fuel, but it may also make excess free radicals as a response to being exposed to toxic things, such as smoking tobacco or drinking too much alcohol.
Over time, we know that damaged cell DNA can cause cancer. This is why many people—doctors and researchers included—have long believed that antioxidants can prevent cancer. But they haven’t been able to prove it in clinical studies, and the new research out today helps explain why.
The body needs antioxidants to neutralize the damaging effects of oxidation, so it makes some itself. But it also counts on getting some from the food you eat (enter the superfoods).
And because antioxidants defend against the cell-damaging oxidation process, they allow cells to grow and thrive—which is a good thing—that is, unless those cells happen to be bad actors (cancer).
Giving Lung Cancer Cells the Green Light to Spread
Genetic mutations can cause lung cancer, which they do by allowing the cancer cells to grow and divide without stopping. According to Dr. Pagano, many lung cancers (particularly non-small cell lung cancers, which make up the majority of lung cancers) have genetic mutations that do this by either turning on a protein that increases antioxidant production or turning off a protein that keeps antioxidant production in check. About 30 percent of non-small cell lung cancers have one of these two mutations, which ultimately (by increasing one particular antioxidant called “HO1”) cause an increase in a protein called “BACH1” that plays an important role in helping cells to spread to other places in the body.
“We know that the oxidative stress, which can come from smoke, radiation, or high cell proliferation, further increases DNA damage; so immediately, one can think that by blocking the stress, you can avoid DNA damage and its subsequent pro-tumorigenic [cancer-causing] effect,” Dr. Pagano said. “Which is probably partially true. But unfortunately, when you block the oxidative stress in lung cancer, indirectly, you are also promoting the accumulation of BACH1, which is a pro-metastasis protein.”
Researchers don’t know for sure why the body originally evolved in a way that links its cell-spreading process to antioxidant production, but one theory, according to the paper’s press release, is that “oxidative stress defenses and migration evolved to overlap so that cells faced with extreme stress locally could migrate in search of a better home.” That is, if something damaging is going on in one area of the body, the cells can go somewhere else.
And while this may be a good thing for healthy cells, when it comes to cancer, you really don’t want your malignant cells to have free rein to go other places. Lung cancer is the leading cause of cancer-related death in the U.S., and most of the time, that death is because the cancer cells have invaded vital organs in other parts of the body that you need to survive.
This description only scratches the surface of the complicated biology that the researchers discovered in the study. But according to Dr. Pagano, the takeaway is that, if you have lung cancer, it’s probably not a good idea to deliberately take excess antioxidants like vitamin E supplements.
So Should I Cut Back on Antioxidant-Rich Foods?
If you’re concerned about the spread of lung cancer, Dr. Pagano said, it’s probably not going to help you to stop eating those healthy antioxidant-rich foods. This could be because the antioxidant levels in foods are too low to have an effect on this process, or it could be because the body processes antioxidants that occur in complex food molecules differently than the pure supplements—and there are no studies so far showing any negative effects of increasing antioxidant-rich food increase. But either which way, Dr. Pagano said, it’s not necessary to cut out superfoods. It could, however, be a good idea to steer clear of the pure supplement forms of antioxidants—like vitamin E or beta-carotene pills—in excess amounts.
“I wouldn’t go taking three doses of vitamin E pills a day,” Dr. Pagano said. “But I would not avoid going so far as to avoid all the foods with antioxidants like tomatoes and fruit and such. Those levels [of antioxidants] are probably not going to do much.”
More Research Is Needed
Importantly, this research was done in both tissue samples outside of the body and in mouse models, and the researchers will need to take the next step of putting their discoveries to the test in clinical, in-human trials. Dr. Pagano said there is also further research to be done about the potential fix for this too-much-antioxidants-helps-lung-cancer-spread problem. The researchers on his team did identify one potential drug in the course of their study, called an HO1 inhibitor, which they think could potentially mitigate this phenomenon, but it’s only ever been used for short-term conditions, and will need to be engineered and tested to be safe for longer-term use.
“We are always happy to discover one more piece of the puzzle,” Dr. Pagano said about how his study’s findings help explain how lung cancer works—and how to stop its spread. “But the more pieces you get, the more you realize how many are missing, and there are so many missing. But one-by-one, ultimately, we’ll get there.”