Continued from Yesterday.....
Is the Medical Community Ready to Accept Antioxidants?
To gain an understanding of the opinions of the mainstream medical community, the most obvious place to turn is the American Medical Association (AMA), which defines itself as the very "voice of the American medical profession." The flagship journal of the AMA is JAMA: The Journal of the American Medical Association, and while the journal's editorials carry a disclaimer that they represent the authors of the journal and not those of the AMA, the content of JAMA nonetheless gives clear insight into the positions, stances and trends of the medical profession. Further, alongside the The New England Journal of Medicine and the British Medical Journal, JAMA is among the premier medical journals in the English-speaking world. Considering all of this, it is not too great of an overstatement to say that it was a monumental event that JAMA and the AMA's nine specialty Archives journals coordinated theme issues last November to provide a forum to present scientific research about alternative therapies to the medical community and the public.
Continually in the Nov. 11 JAMA theme issue, contributors commented on the meteoric rise of the public's interest in alternative medical therapies, which were functionally defined as interventions neither taught widely in medical schools nor generally available in U.S. hospitals (i.e. herbal medicine, dietary supplements, homeopathy, energy healing, acupuncture, chiropractic, etc.). Although acknowledging the popularity of alternative medicine, numerous contributors stated that the scientific research conducted on alternative medical practices has been woefully inadequate.
In an editorial, Phil Fontanarosa, M.D., and JAMA editor George Lundberg, M.D., summarized the opinions of many contributors to the JAMA theme issue. "Despite the increasing use of alternative medicine in the United States and throughout the world, most alternative therapies have not been evaluated using rigorously conducted scientific tests on efficacy based on accepted rules of evidence," the two doctors wrote. "The lack of properly designed and conducted randomized trials is a major concern." Later in the editorial, Fontanarosa and Lundberg again railed, "the lack of convincing and compelling evidence on efficacy, safety and outcomes is unacceptable and troubling."
At the same time, the AMA and the editors of JAMA concede, albeit begrudgingly, that dietary supplements have taken a significant role in the health care choices of millions of Americans. In another JAMA editorial, Wayne Jonas, M.D., concluded, "Alternative medicine is here to stay. It is no longer an option to ignore it or treat it as something outside the normal processes of science and medicine. The challenge is to move forward carefully, using both reason and wisdom, as we attempt to separate the pearls from the mud." This may not constitute an endorsement of dietary supplements and other alternative practices, but it's a start in the right direction.
Keeping in mind the medical community's skepticism toward the amount of conducted research and the efficacy of supplement products, it is not difficult to see that the category of natural antioxidants faces an uphill struggle in gaining unequivocal acceptance among the majority of doctors and pharmacists. At the same time, however, the combination of patient interest and increasing research has led the medical community to become more aware of antioxidant supplementation.
"Doctors certainly are becoming more aware, primarily because their patients are asking them more questions about antioxidants and supplements in general," said Varro Tyler. "But to date, many doctors have not learned about these options in their medical school curriculums, so they are just beginning to find out about them. I would say that there is a small group of doctors that are knowledgeable and have made an effort to understand supplements. Then there is a much larger group that is just in the learning stage and generally very interested but not necessarily well-informed."
Many of those in the minority group of doctors who are knowledgeable about dietary supplements are likely members of the American College for Advancement in Medicine (ACAM). Founded in 1973, ACAM is a non-profit medical society dedicated to educating physicians on the latest findings and emerging procedures in complementary/alternative medicine, with special emphasis on preventive/nutritional medicine. As a listing on the ACAM website at www.acam.org shows, physicians who are members of ACAM can be found in or near virtually every community in the United States. "The number of doctors who take antioxidants and are recommending them is increasing," said Janson, ACAM's president. "For example, if you look at ACAM, doctor membership has doubled twice in the last 10 years. This increasing interest in dietary supplements by doctors is primarily a result of patients demanding to know more about them. Doctors are also forced to look at the overwhelming medical evidence in support of antioxidants."
Janson argued that there are tangible indications that the medical profession as a whole is moving toward recognizing the utility of supplements. One sign is the increasing frequency of medical conferences on topics such as antioxidants, nutrition and preventive medicine. Also, Janson noted the recent publication by Physicians' Desk Reference of PDR for Herbal Medicine, which he characterized as a "revolutionary" occurance. This text is designed specifically for doctors as a review of available information on indications, pharmacological effects, proper dosage, precautions, adverse reactions, symptoms of overdose, along with exhaustive citations from the scientific literature on herbs and botanicals.
Doctors are not the only health care professionals who are being forced to learn more about dietary supplements as a result of public demand. In many cases, pharmacists rather than doctors are being quizzed by the public on supplement options such as antioxidants. One reason for this is that pharmacies across the country are devoting more and more shelf space to dietary supplements, and customers therefore assume that pharmacists have a thorough knowledge of these products. Unfortunately, this is often not the case.
"Natural products were probably covered in courses under pharmacognasy, which mostly has been eliminated from pharmacy school programs in the last 20 or 30 years," said Robert Anderson, Pharm.D., professor of pharmacy practice at Mercer University in Atlanta. "There is still information on vitamins, but a lot of the herbal medications had pretty much gone out of favor in pharmacy school curricula in the late 1960s and early 70s. But there is a trend now where it is coming back, and so I think the knowledge base of the pharmacist is getting adequate. But the difficult thing is trying to assess all this new information that is coming in almost every day, and I think there is a need for more Continuing Education (C.E.) programs in this area."
According to Herrier of the College of Pharmacy at the University of Arizona, many pharmacists realize the need to bone up on their knowledge of herbs and other supplement options. "In terms of C.E. opportunities, topics such as herbal medicines have been really high on the request list, and whenever there is a session on one of these topics, it is extremely well attended and there are a wealth of questions from the audience about specific issues. At the last one I attended, the speaker in fact talked about the respective merits of the individual antioxidants."
Comparing the various substances that have been termed antioxidants appears to be important to pharmacists. Much of this is due to pharmacists', like doctors', emphasis on scientifically validated research. For example, Rex Force, Pharm.D., assistant professor of family medicine and pharmacy practice at Idaho St. University, is careful to differentiate one supplement that has been indicated as an antioxidant from another. "I don't have any problem recommending that people take a supplemental dose of vitamin E. Certainly, for people with cardiovascular disease, it is reasonable for them to take a vitamin E supplement," he explained. "They do not have to be in megadoses--400 or so IUs is appropriate."
Force continued with an evaluation of some other antioxidants. "I don't recommend vitamin A or beta carotene to anyone. Vitamin A/beta carotene has not been shown in prospective studies where it is administered to patients to make a difference. And, in fact, in some studies beta carotene has been shown to be harmful. As far as other antioxidants go, there is really no strong data for vitamin C, particularly with cancer and cardiovascular disease. There are epidemiological studies that suggest diets rich in vitamin C reduces risk for these diseases, but when supplements are used in the studies it doesn't seem to make a difference. I am going to be very conservative about people putting things in their body when we don't know what the long-term adverse or beneficial effects may be. So I am very evidence-based--show me what types of studies have been done and what we really know."
Ziegler of the National Cancer Institute does not find the evidence in support of any antioxidants to be substantial enough to warrant their role at this time against cancers, which is her area of expertise. "I don't think there is any persuasive evidence at the present time that oxidative damage plays a critical role in the genesis of cancers. I also don't feel that there is strong evidence that vitamins E, C and beta carotene protect against cancer by working as antioxidants. I am not saying that they do not, and these are important hypotheses that need further exploration. But they have not been proved or disproved. I am not trying to knock the hypotheses, but I am concerned about making the leap to giving scientific advice to the public on the basis of limited evidence."
However, there can be a range of divergent opinions and interpretations among scientists and doctors of what constitutes "limited" evidence. Some scientists believe that research to date has shown the validity of antioxidants for the prevention and/or treatment of cancer. "Antioxidants have demonstrated positive results in the prevention or alleviation of many chronic and degenerative diseases such as cancer," said Debasis Bagchi, Ph.D., director of research and development at InterHealth Nutraceuticals and adjunct associate professor at Creighton Universitry. "Recent studies at the University of Nebraska in Omaha have found that ActiVin, a proanthocyandin grape seed extract, does more than simply neutralize harmful free radicals. It actually works at the genetic level, increasing the activity of tumor suppressor genes and decreasing the activity of tumor promotion genes."
Differences in awareness of what research is available may also factor into varying opinions about antioxidants. It likely does not come as a surprise that many doctors and pharmacists are out of the loop when it comes to the wealth of research data that is available on some antioxidants. For example, grape seed extract is widely viewed by the medical community as an antioxidant more on the scientific fringe than, say, essential vitamins. For this reason, grape seed extract is often regarded as new and not well tested. But Paulo Morazzoni, Ph.D., scientific director at Indena S.p.A., supplier of LeucoSelect Phytosome--derived from grape seed extract--relates a very different story in which extensive research of every type has been conducted on grape seed extract. In instances such as this one, it may not necessarily be that the research has yet to have been done, but rather that American doctors and pharmacists are not aware of the research that it is out there on an antioxidant substance.
"Plants such as green tea, grape seed and pine bark are all characterized by their content in polyphenols, particularly procyanidins," recounted Morazzoni. "Numerous in vitro studies have shown that procyanidins have been indicated in the test tube to exert a significant antioxidant effect. What makes procyanidins even more interesting, in my opinion, is the in vivo situation, which is mainly due to the fact that these procyanidins are contained in dietary foods. And if you consider epidemiology as the science that can provide information about the linkage between, for instance, the intake of dietary polyphenols and incidence of certain pathologies, what we can say now in a short summary is that there is strong evidence that the dietary intake of certain polyphenols such as procyanidins, because of mostly their antioxidant effect, corresponds to a lower incidence of some diseases."
"There is an additional element in that there have been controlled human studies," continued Morazzoni. "In Europe, going back decades, the product of grape seed extract has been the subject of controlled human studies and shown to improve certain pathological situations in the vascular system. It is this kind of documentation in Europe that has allowed the registration of some grape seed products as prescription drugs."
However, there is almost always a need for more scientific investigation. For example, how exactly proanthocyanidins biochemically impact the human body is not yet known. As Bagchi of InterHealth Nutraceuticals noted, grape seed extract does more than simply quench free radicals. Sevanian of USC recently completed a pre-clinical study on proanthocyanidins and the role they play in the prevention of cardiovascular disease that utilized Indena's LeucoSelect Phytosome. "The more investigation we do on some of these antioxidants, the more we realize that their role is not simply as an antioxidant--that is strictly scavenging free radicals--but that they seem to have fundamental effects on the biochemistry of cells that may be related to antioxidant-type activity but not of the classical nature." Sevanian said there are indications that proanthocyanidins affect the signaling of specific cell membrane proteins that elicit signals into cells that control the cascade of gene expression.
Papas of Eastman Chemical also explained that antioxidant substances work together in the human body, and that it is therefore necessary to not oversimplify and/or draw too broad of conclusions based on research conducted on individual antioxidants. "The relative ability of antioxidants to prevent oxidation in foods or in vitro systems is often extrapolated to their antioxidant function in human tissue," he said. "Because antioxidants act as components of a complex system, comparisons based on a single test or criterion are mostly inaccurate and not very meaningful. Antioxidants should be viewed as a team, where each member brings special strengths. Vitamin C, for example is water-soluble, while vitamin E is fat-soluble. Working together, antioxidants produce synergies, and their combined action is stronger than the sum of their individual potential."
The possibility that antioxidant substances function in the human body beyond simply as antioxidants and that antioxidants act in the body in a complex synergistic manner helps show what scientists have known for centuries: that research findings often raise more questions than they answer. However, any scientist will tell you that this phenomenon almost always indicates that scientific progress is being made. And this is clearly the case in regard to antioxidant substances and their role in the human body
Continued Tomorrow....
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