The essence of a healthy diet is a bit of a mystery. Everyone knows that a diet full of plant foods—fruits, vegetables, and nuts—is good for you, as it can lower the risk of cancer, cardiovascular disease, and other ailments. But scientists, being scientists, want to know the exact reason, and they have long eyed antioxidants. These chemicals, found in high amounts in some plants, quench harmful molecules that can run amok in cells, fatally damaging DNA and the cellular machinery.

As the hypothesis that antioxidants offer health benefits took root in the minds of consumers, however, it shriveled in labs. Mounds of studies, conducted over decades, have found no conclusive link between antioxidants and lower disease risks. And, this month, two studies add to evidence that antioxidants may actually increase the spread and severity of some cancers.

Antioxidants and cancer

When cancer patients first get their diagnosis, many hit the internet to learn more, Martin Bergö, a molecular medicine researcher at the Karolinska Institute, told Ars. But, sadly, patients are often besieged with bogus claims that taking antioxidant supplements, such as vitamin E and beta-carotene, can help treat their cancer, he said. And those antioxidants may end up hurting them.

Earlier this month, Bergö and colleagues reported in Science Translational Medicine that antioxidants can double the spread of melanoma tumors in mice. Last year, his group similarly found that antioxidants can speed the progression of lung cancer.

The simplest way to explain it, Bergö said, is that antioxidants protect healthy cells and cancer cells from the damaging effects of molecules called reactive oxygen species (ROS). These molecules often have unpaired electrons, making them engage in a variety of chemical reactions. ROS are formed as the hazardous waste of normal cellular energy production, although they can also come from external sources, such as radiation.

These molecules, also called free radicals, are desperate to rip electrons away from anything that crosses their path. They engage in ruthless theft from DNA, lipids, and proteins, creating damage that can, in some cases, be irreparable and cause whole cells to die.

When cancer cells break free of their native tumor and roam the body (a process called metastasis), they can face what’s called oxidative stress—an onslaught of ROS. The molecular massacre usually prevents most cancer cells from making it to new organs and tissues. But a shot of antioxidants can spare them, making it more likely that the cancer cells will survive and settle into tumorous outposts.

This is exactly what Sean Morrison and colleagues saw in their study, published last week in Nature. Morrison, director of the Children's Medical Center Research Institute at the University of Texas Southwestern, injected specialized mice with melanomas from human patients. Previous data showed that the cancer's behavior in the mice mimics what the cancers will do in the human patients. When the researchers gave the mice a dose of an antioxidant, it increased the spread of the human cancers.

Though more work needs to be done, Morrison and Bergö expect the results to hold true for other types of cancers. And the findings are actually quite consistent with results from previous clinical trials, Morrison told Ars. Those previous data have just been largely overlooked, he said—probably because “the idea that antioxidants are good for you has been so strong in people’s minds.”

Mixed results

These results have been backed up by some studies in humans, too. In 1994, researchers published results from a double-blind, randomized clinical trail of more than 29,000 Finnish male smokers who were either given antioxidant supplements or placebo. After years of follow up, those given beta-carotene antioxidants had an 18 percent increased risk of lung cancer and an eighteen percent higher death rate. Another large clinical trial of men, published in 2011, similarly found that vitamin E increased the risk of prostate cancer.

But, Morrison cautions, much of those data relate to people who already have cancer or likely have precancerous conditions. They don’t tell us much about risks for healthy people, he said.

Still, there have been dozens of other studies on antioxidants and their effect on everything from cancer to cardiovascular disease and asthma. Early population studies backed up some of the hints that antioxidants might be good for health. But in controlled, clinical trials, the health benefits generally crumbled, with studies presenting conflicting results or finding no connection between antioxidants and disease.

For instance, a population study published in 1991 found that relatively high levels of vitamin E and beta-carotene in people’s plasma linked to lower incidence of cardiovascular disease. But, in a later randomized, placebo-controlled study of more than 20,000 adults, researchers found that those antioxidants had no impact on cardiovascular disease or death.

While the clinical studies fail to show health benefits of taking antioxidant supplements, that doesn’t necessarily translate to the rest of your diet, Morrison cautioned. “People say eat blueberries, and then they hear me say that antioxidants are bad for cancer and they think there’s a conflict. There is no conflict,” he said. It’s one thing to get 100 percent of your daily recommended vitamin dose through healthy eating. But, he said, it’s another thing to take a pill that gives you a thousand times that recommended dose.

Science Translational Medicine, 2015. DOI: 10.1126/scitranslmed.aad3740 (About DOIs)

Nature, 2015. DOI: 10.1038/nature15726