Prevention in a Pill

Originally published in the Fall 2018 issue of Act Against Cancer.

From left to right: Sherry Chow, PhD, Peter Lance, MD, and Elizabeth Jacobs, PhD, are behind milestone clinical trials valuating whether selenium supplements can reduce cancer risk. Photo: Kris Hanning, UAHS BioCommunications

Vitamins and minerals are celebrated for their ability to promote health. Iron staves off anemia, and a collection of B vitamins averts maladies ranging from beriberi to birth defects. In the 1970s, vitamin C supplements enjoyed widespread popularity for their purported power to fight the common cold and even certain types of cancers — although these claims were handily debunked by clinical trials.

The idea that cancer prevention might be found in a pill, easily plucked from the shelves of any grocery store, continues to hold appeal. Additionally, with approximately half of all U.S. adults taking some kind of vitamin or mineral supplement, it is important that scientists conduct the tests necessary to untangle fact from fiction — so that consumers can make the best decisions for their own health.

Clumps, bumps and lumps

Colorectal cancer is foreshadowed by polyps, also known as colorectal adenomas, clumps of cells that form in the colon and sometimes can turn into cancer, but can be detected and removed during a colonoscopy.

“When we do research, there are always more questions raised when it’s done.”

“If you take the adenoma out and put it in the bucket, that adenoma can’t go on to become cancer,” says Peter Lance, MD, professor of medicine and former University of Arizona Cancer Center deputy director – Phoenix and director of the Cancer Prevention and Control Program. “But people who have grown one or more adenoma are at greater risk to develop new adenomas.”

Furthermore, says Sherry Chow, PhD, co-leader of the Cancer Prevention and Control Program, “Reducing the recurrence of colorectal adenomas can reduce one’s risk of developing colorectal cancer.”

The idea that colorectal cancer can be prevented by a proper diet makes intuitive sense. After all, our foods pass through our colons, so it seems plausible that the chemicals in our diets could have positive or negative interactions with the cells they encounter on their journey through the digestive tract. Identifying important dietary compounds has been a source of intense scientific interest.

Early hints

Selenium, a mineral found in water and some foods, lacks the name recognition many other vitamins and minerals have. Most people associate vitamin C with oranges, calcium with dairy and iron with red meat — but they draw a blank when it comes to selenium, although selenium supplements are available in grocery stores and pharmacies. Since the 1990s, researchers at the UA Cancer Center have been at the forefront of investigations into this mineral’s potential for cancer prevention.

Early evidence hinting that selenium supplements could protect against certain cancers led to a burst of studies testing that claim. One such study was the Nutritional Prevention of Cancer Trial, helmed by the UA Cancer Center’s Larry C. Clark, PhD, MPH, which primarily examined the effect of selenium supplementation on non-melanoma skin cancer. Although investigators failed to find a link, they detected something else: a reduced risk of colorectal cancer.

UA Cancer Center nutritional epidemiologist Elizabeth Jacobs, PhD, who worked on the study as a first-year graduate student, remembers the flood of media attention the results received. Suddenly, selenium for cancer prevention was the talk of the town.

“After Larry Clark’s study came out, he told this story that he went into Costco and all the selenium was off the shelves,” Dr. Jacobs recalls. “People had bought it up.” (Dr. Clark passed away in March 2000.)

But the public was reacting to a single study. Was the rush on selenium premature? The question needed more scrutiny.

Digging deeper

Photo: Kris Hanning, UAHS BioCommunications

To learn more about selenium’s possible role in preventing cancer, Dr. Lance opened the Selenium and Celecoxib Trial. His team recruited participants with precancerous polyps, but with no history of colorectal cancer.

After their polyps were removed, says Dr. Chow, “We followed them to see whether those precancerous growths came back.”

The researchers accumulated data over a period of 12 years, but at the end of the trial, selenium supplementation was not associated with an overall reduction in polyps, suggesting it would not be effective for preventing colorectal cancer. The result was a major disappointment for “Team Selenium.”

A closer look at the data, however, revealed the “heterogeneity of treatment effect,” in which different types of people responded differently to selenium depending on factors such as age and medical history. Participants who had advanced colorectal polyps at the beginning of the study were 18 percent less likely to see a recurrence if they took selenium, raising the possibility that selenium could provide a modest benefit compared to people who started out with smaller, less advanced polyps.

On the other hand, the team found that participants who were 63 or older saw a slight increase in Type 2 diabetes. Therefore, while selenium might benefit some people, its effect may be neutral in other people and could be harmful in an older population.

“When we do research, there are always more questions raised when it’s done,” Dr. Jacobs says.

To unravel these mixed results, Dr. Jacobs received a $2 million grant from the National Cancer Institute to delve deeper into the data.

“What I’m looking at now is whether subgroups of people actually did have a favorable response to selenium supplementation,” says Dr. Jacobs. “We’re really drilling down into the factors that might predict your response to selenium.”

Mulling over null results

When studies find connections between an easily accessible dietary supplement and reduction in cancer risk, those results can grab headlines and clear store shelves.

“After selenium had been shown to potentially be effective in preventing cancer, some people just started taking supplements,” Dr. Chow says with a laugh.

However, follow-up studies that fail to confirm these links — those that report “null results” — don’t typically attract the same level of attention. Just as it is essential for us to be aware of different ways to reduce our cancer risk, so too is it crucial to know what strategies are not backed by science.

“So many people are taking selenium,” Dr. Jacobs says. “It is really important to find out whether taking these supplements is a good idea.”

The best way to find out is through a randomized clinical trial, in which some people receive the supplement and others receive a placebo. Participants are followed over time, and the overall health of the supplement group is compared to the overall health of the placebo group to evaluate effectiveness.

“Once you get suggestive evidence, it’s critically important that you do a really rigorous study,” Dr. Lance says. “Before we introduce agents into clinical practice, we need to know they are effective.”

Rather than being healthful or even benign, supplements could cause harm. UA Cancer Center researchers uncovered one such example when they noted the possible link between selenium supplementation and Type 2 diabetes. Other examples abound, including findings that high doses of beta-carotene are associated with increased risk of lung cancer in male smokers.

“There are other stories like that in early chemoprevention trials, where we thought a compound could prevent cancer, but we actually found they increase cancer risk,” says Dr. Chow. “Null results are important for us to understand the risks and benefits of dietary supplementation.”

To supplement or not to supplement

Although some special populations might benefit from supplements — pregnant people, the elderly — Dr. Jacobs believes, for the most part, they’re superfluous.

“People who take supplements are generally the people who need them least.”

“People who take supplements are generally the people who need them least,” she says. “These individuals are already eating a diet high in fruits and vegetables, and are throwing more nutrition on top of that.”

Even in the face of negative evidence, many people will continue to take supplements, feeling they are hedging their bets. After all, vitamins and minerals are a natural part of our diets, so supplements are widely assumed to be free of major risks.

“Many people have a definite belief that dietary supplements are safe no matter how many they take,” Dr. Jacobs says. “But we’ve shown repeatedly that that’s not the case. In food, it is generally safe. When we take stuff out of food and put it into supplements, we take it out of its natural habitat.”

Until more studies are completed, Dr. Jacobs advises consumers to be cautious.

“With regard to the overall effectiveness of dietary supplements, there is really no evidence that they will prevent cancer — and we need more investigation whether they can actually promote cancer growth,” Dr. Jacobs says. “We need to know as much as possible to help people make decisions that are optimal for their health.”

Since her work with the UA Cancer Center’s first selenium trial in the 1990s, Dr. Jacobs has moved onto other research projects, such as investigations into cancer risk in firefighters and the association between vitamin D and breast cancer. With her current work on selenium and colorectal cancer, Dr. Jacobs has come full circle.

“It’s now 20 years later, and we still have these questions,” Dr. Jacobs says. “That’s science — we’re still trying to dig through this.”