01.01.09
In light of the negative findings in some of the latest high profile clinical trials involving dietary supplements, particularly selenium and vitamins C and E, the Council for Responsible Nutrition (CRN), Washington, D.C., and others are suggesting a new direction for the study of these nutrients. To provide some background, the PHS II and SELECT cancer studies published in JAMA (online in December and in print in January) showed that selenium, along with vitamins C and E, do not prevent prostate cancer.
In an editorial, Peter Gann, MD, ScD, of the University of Illinois at Chicago, commented on the “disappointing news” that two major trials (which were “conceived during the wave of hope” of earlier studies suggesting that cancer might be prevented by selenium or vitamin E) showed that neither selenium nor vitamin E produced any reduction in prostate cancer or other cancers. “...single-agent interventions,” he said, “even in combinations, may be an ineffective approach to primary prevention in average-risk populations. It may be time to give up the idea that the protective influence of diet on prostate cancer risk...can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men.”
“On the other hand,” he added, “non-pharmacological dietary prevention of prostate cancer is probably more complex and may involve certain inconvenient truths. Fortunately, no dietary change this profound is likely to be beneficial for prostate cancer alone. If it requires whole foods, extracts or dietary patterns, it may be necessary to give up the reductionist need to know which molecule is most responsible and perhaps give up the notion of placebo controls as well.”
CRN’s Andrew Shao, PhD, vice president, scientific and regulatory affairs, offered some similar points of view. “The very nature of science is that it is an evolutionary discipline—we learn things from one study, and then seek to confirm those results, look in a different direction, or test for even more possibilities,” he said. “Over the past several decades, a series of observational trials resulted in exciting prospects for the benefits of antioxidant vitamins and chronic disease. These encouraging results led the scientific community to conduct the recently released randomized, controlled trials (RCTs), which seemed to be the next logical step.”
He continued, “While everyone—researchers, industry and consumers—would have been thrilled to see the positive findings from observational studies confirmed, this has not been the case. This leads to more intrigue for the scientific community—to try to determine why the results from these recent RCTs are in apparent conflict with the existing body of data.”
One explanation, Dr. Shao suggested, is that the effects of nutrients in the human body are complex and influenced by many variables. Understanding the causality of chronic disease is equally complex. “RCTs may be inherently limited in their capacity to address the unique challenges presented by nutrients and dietary interventions. Nutrients appear to work best in combination with other nutrients, yet RCTs tend to examine effects of unique chemical molecules in isolation—which is how pharmaceuticals work,” he said, adding, “Further, in using RCTs to study nutrition questions, there is the challenge of being able to create a true control or placebo group. For example, in contrast to pharmaceuticals, it is both impossible and unethical to ensure participants in the control group are not exposed at any level to vitamins and minerals.
“This leads us to the question, ‘what should consumers do?’” Dr. Shao continued. “The best advice for consumers is to engage in a lifetime of healthy habits—like not smoking, maintaining a healthy weight, eating a well-balanced diet and appropriately supplementing with vitamins, regular exercise and regular visits to a physician. These appear to be best practices. Vitamins play a vital role in promoting overall general health and filling specific nutrition gaps…[but they] are just one piece of the puzzle, which may be why we didn’t see the results we anticipated from the recent clinical trials.”
For the future, Dr. Shao encouraged the research community and academia to engage in additional studies designed to answer questions about the effects of nutrients on chronic disease and explore the apparent inconsistencies created by the existing research. “Scientists, policymakers, healthcare professionals and consumers alike should continue to question commonly accepted research models, such as: whether the current approach used in RCTs of studying nutrients in isolation is appropriate; whether observational data are adequate to make policy decisions, as is the case with food; and whether we’re studying the appropriate populations or subgroups, with the appropriate dosage and combination of nutrients for the correct length of time.”
In an editorial, Peter Gann, MD, ScD, of the University of Illinois at Chicago, commented on the “disappointing news” that two major trials (which were “conceived during the wave of hope” of earlier studies suggesting that cancer might be prevented by selenium or vitamin E) showed that neither selenium nor vitamin E produced any reduction in prostate cancer or other cancers. “...single-agent interventions,” he said, “even in combinations, may be an ineffective approach to primary prevention in average-risk populations. It may be time to give up the idea that the protective influence of diet on prostate cancer risk...can be emulated by isolated dietary molecules given alone or in combination to middle-aged and older men.”
“On the other hand,” he added, “non-pharmacological dietary prevention of prostate cancer is probably more complex and may involve certain inconvenient truths. Fortunately, no dietary change this profound is likely to be beneficial for prostate cancer alone. If it requires whole foods, extracts or dietary patterns, it may be necessary to give up the reductionist need to know which molecule is most responsible and perhaps give up the notion of placebo controls as well.”
CRN’s Andrew Shao, PhD, vice president, scientific and regulatory affairs, offered some similar points of view. “The very nature of science is that it is an evolutionary discipline—we learn things from one study, and then seek to confirm those results, look in a different direction, or test for even more possibilities,” he said. “Over the past several decades, a series of observational trials resulted in exciting prospects for the benefits of antioxidant vitamins and chronic disease. These encouraging results led the scientific community to conduct the recently released randomized, controlled trials (RCTs), which seemed to be the next logical step.”
He continued, “While everyone—researchers, industry and consumers—would have been thrilled to see the positive findings from observational studies confirmed, this has not been the case. This leads to more intrigue for the scientific community—to try to determine why the results from these recent RCTs are in apparent conflict with the existing body of data.”
One explanation, Dr. Shao suggested, is that the effects of nutrients in the human body are complex and influenced by many variables. Understanding the causality of chronic disease is equally complex. “RCTs may be inherently limited in their capacity to address the unique challenges presented by nutrients and dietary interventions. Nutrients appear to work best in combination with other nutrients, yet RCTs tend to examine effects of unique chemical molecules in isolation—which is how pharmaceuticals work,” he said, adding, “Further, in using RCTs to study nutrition questions, there is the challenge of being able to create a true control or placebo group. For example, in contrast to pharmaceuticals, it is both impossible and unethical to ensure participants in the control group are not exposed at any level to vitamins and minerals.
“This leads us to the question, ‘what should consumers do?’” Dr. Shao continued. “The best advice for consumers is to engage in a lifetime of healthy habits—like not smoking, maintaining a healthy weight, eating a well-balanced diet and appropriately supplementing with vitamins, regular exercise and regular visits to a physician. These appear to be best practices. Vitamins play a vital role in promoting overall general health and filling specific nutrition gaps…[but they] are just one piece of the puzzle, which may be why we didn’t see the results we anticipated from the recent clinical trials.”
For the future, Dr. Shao encouraged the research community and academia to engage in additional studies designed to answer questions about the effects of nutrients on chronic disease and explore the apparent inconsistencies created by the existing research. “Scientists, policymakers, healthcare professionals and consumers alike should continue to question commonly accepted research models, such as: whether the current approach used in RCTs of studying nutrients in isolation is appropriate; whether observational data are adequate to make policy decisions, as is the case with food; and whether we’re studying the appropriate populations or subgroups, with the appropriate dosage and combination of nutrients for the correct length of time.”
