AICR Conference: Warning about Dietary Supplements for Cancer Patients; Provocative Mechanistic Data on Selenium & Folate; New Insights into Vitamin D & Cancer

WASHINGTON, DC—About 57% of cancer patients use multivitamins or herbal supplements along with traditional treatments, but evidence continues to mount that such over-the-counter products—a $22 billion US industry—may be ineffective or even cause harm. So said speakers here at the American Institute for Cancer Research Conference on Food, Nutrition, Physical Activity & Cancer. Barrie R. Cassileth, PhD, Chief of the Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center (MSKCC), urged physicians to question their cancer patients closely about their use of vitamins and dietary supplements. “Our guidelines at MSKCC are for patients not to take dietary supplements during cancer treatment,” she said. “We have to teach our patients that botanicals are unrefined pharmaceuticals.”FigureDr. Cassileth, founding president of the international Society for Integrative Oncology, noted that some supplements can interfere with standard cancer treatments—for example, high levels of antioxidants protect cells from damage, while radiation therapy and chemotherapy aim to damage cancer cells. In addition, supplements such as garlic, ginkgo, ginseng, and vitamin E can interfere with blood coagulation—“Some patients have actually bled out on the operating table,” Dr. Cassileth said. She also pointed to high-dose intravenous vitamin C as a popular alternative treatment—“this is very dangerous.” Another speaker at the meeting, John A. Milner, PhD, Chief of the National Cancer Institute's Nutritional Science Research Group in the Division of Cancer Prevention, warned that not all people respond to dietary supplements in the same way because each person's genetic makeup is unique. Dr. Milner, who chaired an AICR session on supplements and cancer risk, added that dietary supplements can differ in quality and vary from brand to brand, which makes their potential effects even more problematic. Taking supplements to prevent cancer—either by healthy people or cancer survivors—is controversial and results are mixed, according to speakers at the AICR meeting, which was held shortly after the release of the initial analysis of data from the large multi-site prostate cancer SELECT (Selenium and Vitamin E Cancer Prevention Trial), which found no benefit for selenium or vitamin E taken alone or together in preventing prostate cancer. There were also two worrisome trends in the SELECT study, both small and not statistically significant: an increase in prostate cancer cases among the 35,000-plus men over age 50 taking only vitamin E; and a small but not statistically significant increase in the number of cases of adult-onset diabetes in men taking only selenium. Apparent Benefit for Selenium Based on Cellular Mechanisms Still, Karam El-Bayoumy, PhD, Associate Director of Basic Science and Program Leader of Chemical Carcinogenesis and Chemoprevention at Pennsylvania State University's Hershey Cancer Institute, called the case for or against selenium far from closed. His research, he said, has shown a benefit for selenium based on its cellular mechanisms. “Collectively, based on mechanistic studies conducted in our laboratory and others in preclinical systems, it appears that selenium can alter cellular and molecular targets implicated in prostate cancer progression, recurrence, and metastasis, and thus selenium compounds have the potential to promote prostate cancer survivorship,” he said. “Selenium compounds should be considered for further exploration as primary or supplemental treatment options for advanced prostate cancer in addition to their role as chemopreventive agents.” In his studies, he showed that selenium reduced the levels of serum alpha-antitrypsin (ATT), a biomarker of inflammation known to be higher in prostate cancer patients and to correlate with prostate-specific antigen (PSA) levels. African-American men, who are at higher risk of prostate cancer compared with white men, naturally have higher levels of ATT, Dr. El-Bayoumy said. Folate Factors Also at the meeting, Joel B. Mason, MD, Associate Professor of Medicine and Nutrition at Tufts University, said that judging from data on the B vitamin folate (whose synthetic form is folic acid), it is quite likely that it has two faces, one protective against cancer and the second increasing the risk of cancer. Comparing folate to the two-faced Greek god Proteus, Dr. Mason pointed to the public health program of fortifying cereals and other foods such as bread and pasta with folate to prevent neural tube defects in unborn infants. While dietary folate intake can reduce the risk of colorectal cancer by 40% to 60% in people whose families have a history of colorectal cancer, he noted, the vitamin may have a paradoxical cellular growth-promoting effect when given in large quantities to individuals who already harbor existing foci of pre-cancerous or cancerous cells. In this situation folate may be somewhat similar to the beta-carotene form of vitamin A. In the CARET (Beta-Carotene and Retinol Efficacy Trial) of 18,000 men and women who were smokers, beta-carotene was found to raise the risk of lung cancer rather than—as had been hoped—lower it. In an interview, Dr. Mason noted that a colonic adenoma progresses on a continuum from normal to dysplastic to cancerous and that once cells have passed a certain point on this continuum, folate makes them grow faster—and the cells are growing faster anyway. A substantial proportion of the US population is walking around with colonic adenomas and don't realize it, he said. Many of these people are taking folinic acid-containing multivitamins and eating fortified cereals, and thus could be at higher risk if they already have precancerous or cancerous cells in the colon. “We're presently in a very uncomfortable situation, where we're trying to make public policy based on incomplete evidence,” Dr. Mason said. “It's hard to know what our public policy recommendations should be. I tend to be very conservative.” Since colon cancer is primarily a disease of older men and women, he noted, people over age 45 to 50 should “be very circumspect about taking multivitamins or folic acid,” he advised. And if there is a family history of colonic polyps, “I would be very averse to putting them on a folate supplement.” The AICR is on record as recommending against taking supplements to prevent cancer. But the organization, like the speakers at this meeting, recommends eating more of a variety of vegetables and fruits, which have never been shown to be harmful and may be protective against cancer. Vitamin D Receptor Evidence continues to mount that vitamin D may be protective against cancer, and now some of the mechanisms for that protection may be emerging, said John H. White, PhD, Professor in the Department of Physiology at McGill University. The vitamin D receptor, a ligand-regulated transcription factor, can directly stimulate the function of FoxO proteins, transcription factors that regulate cell cycle progression and are often inactivated in cancer. In animal studies, he said, the loss of FoxO function leads to spontaneous tumor formation, indicating that the proteins are tumor suppressors. Signaling of the active form of vitamin D through the receptor induces the function of FoxO proteins, providing a molecular basis for the cancer chemoprotective actions of vitamin D, he said. And Daniel D. Bikle, MD, PhD, Professor of Medicine and Dermatology at the University of California, San Francisco, reported that his studies have led to the hypothesis that the vitamin D receptor functions as a tumor suppressor with respect to epidermal tumor formation in response to UV radiation from sunlight. “Because the skin is the major source of vitamin D for most individuals, sunlight avoidance has resulted in widespread vitamin D deficiency” as people stay out of the sun and use sunscreens to ward off skin cancer, he warned. Sunlight exposure has become highly controversial because of concerns about skin cancer; human beings obtain vitamin D either through exposing the skin to sunlight or through fortified milk and foods. Unfortunately there is as yet no optimal level of regular sun exposure that has been determined to pose no or little risk of skin cancer, noted Mary Frances Picciano, PhD, Senior Nutrition Research Scientist at the NIH Office of Dietary Supplements. Faced with expert opinions that the current recommended daily intake for vitamin D (400 international units for adults) is too low, the government is reconsidering that intake. But Dr. Picciano noted that several questions remain to be answered, including how to ensure that measurement of vitamin D blood levels is accurate and consistent. As for vitamin D supplements, they can be toxic in high quantities, she added. www.oncology-times.com

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