News from the Field

The Big Impact of Small Nutrients:
The Role of Micronutrients in Cancer Prevention Highlighted in Annual Lecture

On March 19, 2013, Dr. Susan Taylor Mayne (Yale University) gave this year’s Stars in Nutrition & Cancer lecture, presenting research about micronutrients and cancer prevention. Stars in Nutrition & Cancer is a lecture series hosted by the Nutritional Science Research Group in the Division of Cancer Prevention. These lectures feature outstanding scientists or “stars” discussing the latest research about the role of nutrition in cancer prevention and progression.

Dr. Mayne began her talk with an overview of clinical trials that have helped frame our current understanding of micronutrients and cancer. Micronutrients are substances that our bodies require in small amounts and are essential for good health. Vitamins and minerals are examples of micronutrients. Studies have suggested that eating foods rich in these nutrients (particularly fruits and vegetables) is associated with a decreased risk of developing cancer. For example, a review published in 2012 suggested that individuals with high levels of carotenoids in their blood (such as beta-carotene found in carrots and lycopene found in tomatoes) have a lower risk of developing breast cancer. Earlier animal studies of cancer indicated that supplementation may provide similar benefits as eating antioxidant-rich foods, and that set the stage for human trials.

One of the first human studies examining micronutrient supplementation and cancer risk was conducted in a micronutrient-deficient population in China. The results, published in 1993, showed that participants who took the study supplement (a combination of beta-carotene, vitamin E, and selenium) had a reduction in cancer deaths. A follow-up study published in 2010 showed that benefits remained, even 10 years after participants stopped taking the supplements. However, studies published in the mid-1990s found that beta-carotene supplementation was associated with an increase in cancer deaths. Further analysis of those results revealed that the supplement doses used may have been too high for many of the study participants and that supplementation was beneficial in people who were deficient in a specific nutrient. Dr. Mayne noted that this pattern is not exclusive to beta-carotene — similar findings have been shown for selenium and folic acid as well.

Results of studies investigating the relationship between micronutrient status and chronic diseases, such as cancer, consistently show a U-shaped curve: disease risk decreases as nutrient levels increase, although at a certain point, at higher levels of nutrient status, disease risk starts to go back up. These findings indicate that nutrient supplementation may not help individuals who have high levels of a certain nutrient, rather, the greatest benefits may occur for those on the lower end of the curve.

Dr. Mayne then spoke about new technology being used in her lab that quickly determines an individual’s micronutrient status and can help identify individuals who have low levels of specific micronutrients. Resonance Ramen Spectroscopy (RRS) uses a small laser to deliver light to an area of the skin. Carotenoids in the skin vibrate when they are hit with a specific wavelength of light and those vibrations indicate carotenoid levels in the skin. Carotenoids accumulate in the palm of the hand and that is where the light is directed.

Dr. Mayne described how this biomarker was developed. Accuracy of this method was determined by comparing the RRS information to data obtained from skin biopsies. In that study, hips were scanned and small skin samples were taken for analysis. Feasibility studies were also conducted, including one in preschool children. Children from a low-income area were scanned with the RRS and carotenoid levels were compared with fruit and vegetable intake and preference (this information was provided by parents). The data obtained from the RRS scan was significantly correlated with the intake and preference measures. Dr. Mayne also presented unpublished data that showed that the carotenoid levels obtained from RRS responded to a dietary intervention — for example, levels increased when subjects ate carotenoid-rich foods and decreased when subjects ate a low-carotenoid diet.

There is a lot of evidence that micronutrient status may affect cancer risk, but Dr. Mayne suggests that future clinical trials using supplements should target populations that have a low nutrient status, as those individuals may get the most benefit out of supplementation. Using technology, such as the new biomarker she described, may help to identify those individuals.

For more information or to view past lectures, visit http://prevention.cancer.gov/programs-resources/groups/ns/events/stars.

Probiotics, Prebiotics, and Synbiotics, Oh My

The Nutritional Science Research Group at the Division of Cancer Prevention hosted a webinar titled “Exploring the Microbiome of Cancer Prevention: A Closer Look at Probiotics, Prebiotics, and Synbiotics.” The microbiome is made up of the microorganisms, including bacteria and fungi, which we carry inside and outside of our bodies. These microorganisms do not normally cause disease, but work in harmony with our bodies and are involved in many processes that contribute to our state of health. Recent studies have suggested that microbes in our gut may be involved in cancer prevention and the webinar highlighted work in that area.

The first presenter was Dr. M. Andrea Azcarate-Peril, Ph.D., RD (University of North Carolina-Chapel Hill), who spoke about the role of probiotics in preventing and treating colorectal cancer (CRC). Dr. Azcarate-Peril defined probiotics as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” While the concept of probiotics has been around since the early 1900s, the tools and technologies for microbiome analysis have been recently developed. Dr. Azcarate-Peril observed that “next generation sequencing approaches have permitted the analysis of the structure of microbial communities and a number of different types of analysis.”  

A few studies have compared the microbiota of healthy patients with CRC patients. Dr. Azcarate-Peril noted there was only one study that compared the microbiota in healthy intestinal mucosa with mucosa from adenomas (a pre-cancerous growth in the colon). “We showed that changes in the tumor microbiota started really early in the progression to carcinoma,” she said. Studies have indicated that intestinal microbiota may produce toxic bacterial metabolites that can lead to mutations and CRC. Dr. Azcarate-Peril described a recent study that showed that CRC patients had higher levels of a certain intestinal microorganism than did healthy controls, suggesting that it may be possible to create tailored probiotics to help prevent cancer. However, Dr. Azcarate-Peril mentioned that there “is no general consensus on the role of probiotics in CRC protection.” Some reasons for lack of agreement include different methods of preparing probiotics, and using various blends and doses of probiotics.

“Prebiotics and Their Role in Cancer Prevention” was the title of the presentation by Joanne L. Slavin, Ph.D., RD (University of Minnesota). She began her talk by describing the gut as a functional ecosystem and mentioned that, in addition to diet, some things that can change the make-up of microbes in the gut include stress and living conditions. Prebiotics are selectively fermented ingredients that improve health by changing the composition and/or activity of microorganisms in the colon. Examples of prebiotics include a class of dietary fibers known as fructans. Fructans are found in a number of foods such as artichokes, wheat, onions, and chickpeas. Dr. Slavin noted that in the United States, wheat is the main source of fructans. Prebiotics are also found in many fiber-fortified foods. According to a recent review, prebiotic administration was not associated with changes in CRC biomarkers. However, Dr. Slavin stated that “one of the conclusions from the study is while we cannot agree on what is a prebiotic and what are the best methods to measure microbiota, progress in this field is going to be difficult.”

Ian Rowland, Ph.D., RD (University of Reading, United Kingdom) spoke about synbiotics. Synbiotics are mixtures of pre- and probiotics that provide benefits to the host by improving survival of microorganisms in the gut by stimulating their growth and/or metabolism. Dr. Rowland noted, “In other words, it’s a matter of combining pre- and probiotics with the aim of getting a benefit that is greater than from pre- and probiotics alone.”

There is evidence that synbiotics may play a role in preventing cancer or slowing disease progression. Dr. Rowland described results of a study that investigated the effects of synbiotics on a rat model of CRC. In that study, rats were fed diets supplemented with a probiotic, a prebiotic, or a combination of the two. Compared to rats that were fed a normal diet, the probiotic- and prebiotic-fed animals exhibited a lower number of aberrant crypt foci (early changes in the colon which may lead to CRC) in the colon. The animals that received the synbiotic supplement showed the least amount of pre-cancerous changes in the colon. In a clinical trial, patients at high-risk or with a history of CRC received a synbiotic supplement or placebo for 12 weeks. Biopsies and stool samples were assessed for biomarkers of CRC risk. Results indicated there was less DNA damage and cell proliferation in biopsies from subjects who received synbiotics compared to subjects taking the placebo, suggesting synbiotics may have a protective effect. The exact mechanisms underlying these effects are not known, but animal studies have suggested that synbiotics may increase levels of protective enzymes in the gut and may increase programmed cell death (apoptosis) in aberrant crypt foci.

This webinar was part of the “Frontiers in Nutrition and Cancer Prevention: Online CME Series.” For more information about this series and to view archived webinars, visit http://prevention.cancer.gov/programs-resources/groups/ns/webinars/.