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The ultimate in “integrative medicine”: Integrating the unscientific into the medical school curriculum

For the second week in a row I find myself throwing out the original post that I had planned on doing in favor of a different topic. The reason this week is, quite simply, having read Dr. Atwood’s excellent two part post Misleading Language: The Common Currency of “CAM” Characterizations (Part I; Part II). I don’t at this time intend to expand on what Dr. Atwood said, although I may do so at one future time. What caught my attention in his lengthy deconstruction was his segment on the “woo-ification” of health care, which very much echoed my post a while back in which I lamented the creeping infiltration of non-science-based modalities into academic medical centers, as well as the credulous teaching of such modalities in medical schools. What I wanted to explore was just how far this might go and what the end result might be. It turns out that we are already witnessing an experiment in just such a thing.

About a year and a half ago, I first became aware of just how far this infiltration of unscientific “medicine” has infiltrated academia when I saw this brochure published by the Georgetown University School of Medicine. If you’re scientifically inclined, as I am, it ought to make you shudder. Reading this brochure, I truly have to worry whether woo really is the future of American medicine, as has been suggested in some quarters. Certainly, if other medical schools start following Georgetown’s lead, it will be. Not content to offer so-called complementary and alternative medicine (“CAM”) modalities as part of electives that interested students can take if they are so inclined, Georgetown is taking the next logical step that I feared: It’s dedicating significant educational resources and time to teaching “CAM” in its mandatory general medical curriculum, where every student has to learn it:

Figures on how medical schools are introducing CAM education are less definitive. Another study published in JAMA in 1998 reports that 75 of the 117 participating U.S. medical schools offer CAM elective courses or include CAM topics in required courses.

“One of the reasons CAM is usually offered as an elective is that there’s just no time or room in U.S. medical schools to fit in one more massive subject,” says Michael Lumpkin, Ph.D., professor and chair of the department of physiology and biophysics at Georgetown. “When the course is an elective, a self-selected group – maybe 10 or 20 students in a class of 180 medical students – will take it,” Lumpkin says. “What we’ve tried at Georgetown is rather than create all new courses, we take relevant CAM issues and modalities and weave them seamlessly into existing courses.

The “seamless” weaving of CAM into existing classes includes, for instance, a presentation by an acupuncturist on the “anatomy of acupuncture” in the gross anatomy course for first-year students. The same lecturer explores acupuncture’s application in pain relief in the neuroscience course…

Haramati and Lumpkin say Georgetown’s program is distinct from CAM initiatives in other medical schools in two ways: The school is integrating CAM education into existing course work across all four years of each student’s medical education, and the initiative includes a mind-body class to help students use techniques to manage their own health and improve self-care.

Teaching the “anatomy of acupuncture” in formal anatomy classes that every medical student has to take and pass? Great. Heck, why not teach “intelligent design” creationism in basic biology classes while they’re at it? It would be the same idea: Mixing nonscience with science. Next they’ll be teaching Samuel Hahnemann’s “principle of similars” and concept of homeopathic dilution in biochemistry and pharmacy classes! Or maybe they’ll teach about qi in physiology or neurology. In fact, Georgetown’s program is actually coming close, as it is teaching a veritable cornucopia of unscientific methods: the anatomy of acupuncture; stress hormone modulation in physiology; “mechanisms” of acupuncture action in neuroscience; and psychoneuroimmunology in immunology courses. In fact, it’s worse than that. Not only is this sort of material being taught in elective courses, but it is being “integrated” into every aspect of every year of the four year curriculum:

The first year will include an introduction to CAM practices in ambulatory care. In the program’s second year, Georgetown aims to double the number of mind-body session groups and introduce CAM-related issues in lectures in the pharmacology, microbiology, and pathology courses in the students’ second year of medical school.

A CAM elective will also be offered to fourth-year students. Between year two and three of the program, a biomedical research component for students will be introduced; in the remaining years, CAM will be further integrated into the rest of the preclinical courses and most of the clinical clerkships.

“We welcome the medical students to participate with us in conducting those research projects,” Lumpkin explains. “If students get involved in these research projects, it will allow them to go to the cutting edge of CAM. They will become the thought leaders in this field.”

In other words, they will become advocates for non-science-based medicine–exactly what medicine doesn’t need. This is ironic, given that it has been pointed out that “CAM” is actually losing favor in China, where many of the concepts of traditional Chinese medicine that underlie large swaths of alternative medicine originated. Here the same concepts are taking over the medical school curriculum. Here are the principles behind the project:

1. Aim CAM curriculum at all students through required courses.
2. Integrate material into basic science courses.  For example:
Gross Anatomy: anatomy of acupuncture
Human Physiology: biofeedback, neuromuscular manipulation
Human Endocrinology: stress hormone modulation (relaxation response, meditation, imagery, breathing regulation)
Neuroscience: mechanisms of acupuncture action
Immunology: psychoneuroimmunology
3. Begin on the first day of school, if possible.
4. Address knowledge, skills and attitudes regarding CAM.
5. Change culture by evolution not revolution

And Georgetown’s rationale for integrating such practices so deeply into the curriculum strikes me as disingenuous:

Haramati realizes that some mainstream medical practitioners remain skeptical of CAM due to the perception that such therapies lack the rigorous scientific testing that traditional therapies undergo. That’s why exposing medical students to CAM practices and principles is so important, he says.

“Perception”? It’s not just a “perception.” The vast majority of CAM therapies do lack rigorous scientific testing that mainstream medical therapies must undergo. That’s a fact, not a “perception.” So what is Georgetown’s solution? Integrate them into the curriculum because they’re not scientifically validated? That’s putting the cart before the horse! “CAM” therapies needs to be validated through science first. In fact, the purpose of medical school is to teach medical students the basics. There’s little enough room in the curriculum to teach them that. No compelling case that I have yet seen has been made that CAM methodologies are so compelling in their efficacy that room must be made in the mandatory medical school curriculum for them.

Georgetown does, however, give one reason that’s semi-reasonable:

“Rather than to say ‘there’s no data here, why teach it?’ we need to inform our students as much as possible about the therapies that are out there … ‘what does the research tell us, which are useful, which are dangerous’,” Haramati explains. He is also quick to note the initiative is not a program of advocacy. “We’re not teaching a belief system or teaching students to practice CAM, but rather we’re informing students about CAM.”

My retort would be that it’s not necessary to integrate this sort of woo deeply into the curriculum in order to accomplish this. For the vast majority of CAM therapies, a brief overview would be all that is needed. It is not necessary to teach “acupuncture points” in regular anatomy class, particularly when there is no evidence that these points mean anything on a strictly anatomic and physiological basis. The organizers of this curriculum also point out that many people take herbal remedies and dietary supplements, many of which can interact with standard drugs, and cite this as a justification for teaching CAM. That is perhaps their best argument, but my retort would be that it’s not necessary to integrate various non-herbal aspects of CAM into the curriculum to accomplish this. In pharmacology class, all that would have to be done would be, when teaching drug interactions, to include herbal remedies and supplements among the compounds and drugs that can interact with each new medication that is discussed and perhaps include a module on such remedies. Drug interactions are a very important topic, and It is not necessary at all to integrate woo into the medical school curriculum to warn future physicians of what herbal medicines might interfere with various drugs.

As for not being a program of advocacy, if that’s the case, then why is Georgetown not only teaching but also actively encouraging the use of “mind-body” skills that may or may not have any scientific basis by its own medical students? Why does its program tout that it will be starting to teach CAM from the very first day of medical school, as described in on the Georgetown website and brochure. This is what I’m talking about:

Year one of the five-year grant began in fall 2001, with CAM lectures integrated into basic science classes. In winter 2002, educators are introducing a new workshop, “Mind-Body Medicine: An Experiential and Didactic Introduction,” which includes topics on a wide range of mind-body approaches, including meditation, nutrition, physical exercise, relaxation, and self-awareness. Students meet in three or four groups of eight to ten people each.

“Over the next five years we’ll be training additional faculty facilitators,” Haramati says. “Then they’ll form their own groups until the entire medical school class is exposed to the utilization of mind-body skills.” “The idea is to help students with the stress of the intense course of study and expectations that come with medical school,” Lumpkin adds. “By learning their own techniques of self-care, students will naturally internalize that and then be able to use it with their patients in the future. This is a skill physicians generally lack because it’s something they were never taught. In some cases it was debunked as being nonsense. Now there’s a new view of its usefulness.”

Let’s see. Georgetown is teaching “mind-body” medicine to its medical students and actively encouraging them to use it, all in the context of teaching other areas of woo. Sure, the faculty claim that they will be teaching students to “critically assess” the various CAM modalities, but you’ll excuse me if I remain skeptical. As I’ve pointed out before, such programs may start out with the best of intentions with regards to a critical assessment of the evidence (or, in the cases of most CAM, the lack of evidence for its efficacy). However, over time, these things tend to develop a momentum of their own. They also tend to get taken over by true believers. This is probably because most doctors committed to EBM just aren’t that interested in CAM because there’s not much good evidence for the vast majority of modalities that fall under its label and because so many CAM modalities are associated with spiritual/religious concepts underlying them that have no business in science. Moreover, advocates of CAM tend to be much more passionate about promoting it than skeptics are about expressing their skepticism about it. Indeed, if they do, they often are labeled as “close-minded” or “intolerant.”

Like the program at the University of Michigan, the CAM program at Georgetown is funded by a grant from the National Center for Complementary and Alternative Medicine (NCCAM). And here’s where we come to the most pernicious effect of all of NCCAM. The problem is that NCCAM doesn’t just fund grants to study CAM, which, although it often leads to studies of dubious scientific merit about therapies lacking even scientific plausibility, much less data, at least is an intellectually and scientifically defensible endeavor. Unfortunately, NCCAM goes beyond this and funds grants to promote the teaching–indeed, the integration–of CAM in medical schools before these modalities are scientifically proven. Once again, this putting the cart before the horse. The usual order of things in medical education is that modalities to be included in the medical curriculum must first have considerable evidence of efficacy such that they are considered standard of care. Medical school is where students learn the basics. During the first two years they learn the well-established basic science, and during the second two years they learn how to take care of patients according to the standard of care. Then they go on to residency, where they expand on the basics and progress to more advanced education in their therapy. The topics and therapies that Georgetown is integrating into its curriculum are neither well-established science nor the standard of care. Teaching unproven CAM modalities so extensively in the core medical school curriculum rather than as electives is neither scientifically nor educationally appropriate, as it puts the imprimatur of scientific medicine as represented by medical schools on therapies that are anything but scientific.

The virus is spreading.

Depending on what Dr. Atwood decides to write, next week I may take a look at the issue of Academic Medicine from October 2007 and examine some of what has been written there in more detail about the teaching of “CAM” in medical school.

Posted in: Medical Academia, Science and Medicine

Leave a Comment (65) ↓

65 thoughts on “The ultimate in “integrative medicine”: Integrating the unscientific into the medical school curriculum

  1. Aaron S. says:

    Wow, this is just getting ridiculous. It is disappointing when even academic environments starts to try to set these kind of trends.

    Any why does taxpayer money have to fund CAM??? I keep thinking that more and more.

  2. starflyer says:

    Thank goodness I’m at a med school where CAM was handled more skeptically. Our lecture on herbal medications was titled “The Great American Medicine Show.”

  3. overshoot says:

    During the first two years they learn the well-established basic science, and during the second two years they learn how to take care of patients according to the standard of care. Then they go on to residency, where they expand on the basics and progress to more advanced education in their therapy. The topics and therapies that Georgetown is integrating into its curriculum are neither well-established science nor the standard of care.

    Ah, but they will be. Once enough practicing MDs are taught these principles and practices, once enough experts in the field are available to testify as expert witnesses, etc. then anyone not with the program will become heterodox. The woo will become “well-established basic science” simply by virtue of its being taught to everyone as though it were, and the standard of care likewise.

    To a first approximation it doesn’t matter whether it’s planned that way or just the working of broader dynamics (e.g. the increasing influence of religion and sociologically similar forces in American society.) Regardless of root causes, that’s the trend.

  4. Apreche says:

    Aren’t these medical schools accredited? Who does the accrediting? Can’t they just revoke their right to hand out MDs? Do you think it would be justifiable to remove accreditation for medical schools teaching the woo?

  5. daedalus2u says:

    I suspect it is all about money. Teaching CAM must bring in more money. Exactly how I am not sure, but if it didn’t there is no way it would get a foothold.

    The only thing that the administrators are going to listen to is money. They are only going to abandon teaching woo if the cost to teaching woo is higher than the profit.

    The vast majority of MDs from good medical schools have to be opposed to the teaching of woo because it isn’t evidence based and isn’t consistent with the standards of care. If those MD graduates sent letters to the schools they graduated from saying no more donations while woo is being promoted, and that instead their donations would go to non-woo promoting competing schools, I think the promotion of woo would stop. If it didn’t, then at least non-woo schools would get stronger and the woo schools would get weaker.

    If all the schools promote woo, then it does become the “standard of care”. If even a few don’t, then those few can always be pointed to and used as the “real” standard. If the non-woo schools get the bulk of the donations from non-woo practicing MDs, those non-woo schools will persist and become stronger.

    The presence of woo in the curriculum should count against a school in accreditation, and in the awarding of research grants.

  6. Antono says:

    This sounds like a bad joke but April Fool’s day is still two weeks away.

    Especially the part “In the program’s second year, Georgetown aims to double the number of mind-body session groups and introduce CAM-related issues in lectures in the pharmacology, microbiology, and pathology courses in the students’ second year of medical school” read like some parody Mark Crislip would write. I can’t believe this BS was written by a US medical school, it’s ridiculous.

    Just like other members have pointed out, I too believe the USA should be regulating more carefully its medical schools and start removing accreditation from schools with unscientific curriculum.

    But Education in general is also partly to blame. Why do we allow such gullibiliy among the people and even among college graduates? Why don’t medical students revolt at the absurdity of what is being taught to them? Education today is about stuffing minds with facts, not about raising critically thinking individuals.

    Yes, the virus is spreading and it may not be long until woo becomes standard treatment. But do not despair for this will also be its doom: with ever increasing numbers of patients “treated”, the media will be full of failures and side-effects and the public will turn once again to good old medicine… only to go back to CAM when all that travesty will have been forgotten. Going in circles unless we get our Education right.

  7. apteryx says:

    Starflyer wrote:

    “Thank goodness I’m at a med school where CAM was handled more skeptically. Our lecture on herbal medications was titled “The Great American Medicine Show.””

    That’s clever, but if you walk away from your med school with, let’s say, the opinion that ginger can’t possibly help morning sickness but has been proven to interact with warfarin, a subset of your patients will be better informed than you are and will know it. Since most people aren’t aware of MDs’ limited sources of information, they’ll assume that your ignorance is a deliberate choice on your part, probably arising from strong negative opinions of the subject. If they continue to employ your services, they will stop telling you about their use of herbs, assuming that any attempt to inform you will be met with scorn and possibly worse care or pejorative notes in their charts. Although proven drug-herb interactions are far rarer than you are probably taught, they do exist, so this creates a potential safety issue. Have you considered how to avoid presenting a paternalistic or hostile impression to future patients?

  8. DavidCT says:

    Much of the information taught in the first years of professional school is presented from authority without much critical analysis.
    The evaluation skills are often not part of the curriculim. CAM then becomes just something more to learn for the tests.

    Think about the effort it must take to learn all the symptoms and matching homeopathic medications one must learn during training as a homeopathic “physician”. In addition the student has to learn all the dilutions and the ritualistic shaking – when to tap with a leather bound book and when not. Once one goes through all this learning how easy is it to realize rationally that it is all just distilled water. Any wonder that you create true belivers in woo.

    How easy is it really for even EBM people to change their minds about pet beliefs even when new evidence is published. With the amount of art in medicine, early teaching of woo cannot be a good thing.

  9. delaneypa says:

    As a 2001 Georgetown Medical School alumnus, I just missed the woo-ification of my alma mater, thankfully. Georgetown has always had a reputation far better than it deserves (reminds of of the medical student in “House of God” from the “very best medical school”). One year, it was noted that DC public schools had better equipped science laboratories than did Georgetown University. My wife received as good a medical education as I, through a public medical school at 1/10th of the tuition.

    I am indeed disappointed. Next time Dean Mitchell asks me for my $500 annual contribution (“suggested minimum”) I will instead send a copy of your excellent article as a way explanation about why I won’t be sending any more money.

    Georgetown University has a few peculiarities you may not know about. It is a Jesuit institution, beholden to the teachings of the Catholic church. Frocked priests roam the hall of the medical school, and there are some with PhDs research in biology, and several Jesuit MDs.

    Part of the “Jesuit philosophy” we were told at the very beginning of our training was to approach a problem from as many conceivable directions as necessary. Though hardly religious myself, it sounded good to me at the time. Thus, Jesuit philosophy may be playing a role in the woo-ification you outlined above. Even the dean of the medical school has his Jesuit masters.

    It is just a shame that they are cutting cutting down on proven scientific methods to pander to the woo-meisters.

  10. Joe says:

    Apteryx wrote “That’s clever, but if you walk away from your med school with, let’s say, the opinion that ginger can’t possibly help morning sickness but has been proven to interact with warfarin, a subset of your patients will be better informed than you are and will know it.”

    Or, perhaps they will just ‘imagine’ they know better; as you seem to do. The research on ginger vs. morning sickness is inconclusive. Moreover, there is no evidence for the safety of the fetus if the mother takes excessive amounts of ginger (more than is used to spice food). Your, apparent belief that ginger is known to work against nausea indicates that you are not well-informed.

    A well-informed doctor, who was not taught quackery as if it were real, would research your claims. Your suggestion that a good medical education leads to the opinion “that ginger cannot possibly …” is an invalid Straw Man.

  11. apteryx says:

    There are half a dozen human trials for morning sickness, all positive, plus a vast amount of human experience saying that ginger relieves nausea. Maybe that is not “knowledge” to you, but it is certainly suggestive evidence. Perhaps as a well-informed doctor, you will go look up the clinical trials.

    As for your speech about “no evidence” for the “safety of the fetus,” well, again, there are half a dozen clinical trials with no safety problems, plus a total lack of anecdotal harm. You reflect an ethnocentric viewpoint, not only in terming traditional means of symptom relief “quackery,” but in terming a capsule or two of ginger “excessive” because it is “more than is used to spice food.” The fact that your native cuisine disdains pungent flavors and uses pungent vegetables in minuscule quantity does not mean that those plants are dangerous. Asians, including females, commonly eat this plant as a food and drink it as a beverage, often consuming more than a gram per sitting. There is no evidence whatsoever that this impairs their reproduction.

    You have chosen to claim that I put up a straw man, or “Straw Man,” by suggesting that you might tell your patients with morning sickness that ginger could not help them. But your words above suggest that you would discourage them from using it, pooh-poohing any evidence in its favor, and that if they openly disagreed with you, you would call them “not well informed” and club them with the completely unsupported threat of danger to their embryos. That’s paternalism of the plainest kind. It also makes me wonder: would you try to pressure pregnant women of Asian origin to abandon their traditional cuisines, to the extent that those include flavorful plants in greater amounts than [you] used to spice food? I have heard of American pediatricians pressuring immigrant mothers to feed their toddlers unspiced pablum; please tell me you wouldn’t plan to extend that down to the zygote stage!

  12. Joe says:

    Apteryx “Perhaps as a well-informed doctor, you will go look up the clinical trials.”

    I did, as I said, they are inconclusive. Perhaps you can cite some that are compelling.

    Apteryx “As for your speech about “no evidence” for the “safety of the fetus,” well, again, there are half a dozen clinical trials with no safety problems”

    Another half-dozen experiments (I suppose you will cite them)! The data is underwhelming. What sort of harm could they have identified?

    Apteryx “But your words above suggest that you would discourage them from using it …”

    Your ability to “read for meaning” is failing you as badly as your ability to read my mind. Whence do you derive your thoroughgoing inabilities?

    The bottom line remains: medical professionals need to look at science-based treatments, not your wishful thinking and anecdotes. If you can present compelling evidence that ginger is safe and effective, it will become ‘medicine.’

    On the other hand, what would it take to convince you ginger is not safe and effective? Most members of pseudomedical cults cannot relinquish their beliefs. Are you one of those?

  13. David Gorski says:

    There are half a dozen human trials for morning sickness, all positive, plus a vast amount of human experience saying that ginger relieves nausea.

    Please cite them.

    You may be correct, but I would like to judge for myself.

  14. pec says:

    [Georgetown is teaching “mind-body” medicine to its medical students and actively encouraging them to use it, all in the context of teaching other areas of woo.]

    Are you kidding? It is well known that mental states can influence physical health. We know that meditation, or relaxation, can decrease stress, and we know that excessive stress can be harmful to the body.

    If physicians are going to advise patients in makes perfect sense to educate them in relaxation techniques. A physician who knows nothing about health except which drug to prescribe, or what diagnostic and surgical technology to use, is incomplete as a health expert.

    Medicine is, or should be, more than just chemicals and technology. The mind IS an important factor, and this has been demonstrated by research.

  15. PalMD says:

    Why don’t med schools teach mesmerism? Humors? Various forms of shamanism? Voodoo?

    Because there is no evidence to support them, just like all the other cult medicine garbage.

    We do, however, need doctors who are literate and can speak about non-medical pseudo-healing, so that they can approach conversations with their patients from knowledge.

    If we start teaching “CAM” as legitimate medicine, there is no end to the garbage we will force medical students to learn. Given how hard medicine already is to keep up on, maybe we should consign it to the trash-heap of intellectual history.

  16. daedalus2u says:

    I just had a thought, could these woo based healing systems be classified as “religions”? On the one hand it would give them tax exempt status, on the other hand it would be a lot easier to justify not teaching them.

  17. Harriet Hall says:

    There’s a good review article on ginger at: http://www.aafp.org/afp/20070601/1689.html.

    A Cochrane review concluded that it is effective for nausea of pregnancy. The Natural Medicines Comprehensive Database rates it “possibly effective” and warns:

    Using ginger during pregnancy is controversial. There is some concern due to preliminary evidence that ginger might affect fetal sex hormones and an anecdotal report of spontaneous abortion during week 12 of pregnancy in a patient who used ginger for morning sickness. However, studies in pregnant women suggest that ginger can be used safely for morning sickness without harm to the fetus. As with any medication given during pregnancy, the potential benefit to risk.

    Does anyone remember Bendectin? It was a safe, effective morning sickness treatment that we used for years. It was taken off the market because of junk science lawsuits, and a lot of women ended up taking remedies that were potentially more dangerous. All it was was B6 and doxylamine, both available over the counter. I remember it as a glaring example of the triumph of legal paranoia over science.

  18. Hi Dave,

    I won’t be addressing the Oct. ’07 Acad Med “theme” issue, so have at it.

    Regarding ginger and morning sickness, there is a bit of evidence favoring it but the studies are small and the effect modest, if it really exists. It also appears to be safe in pregnancy, but this is not certain:

    http://www.ncbi.nlm.nih.gov/pubmed/1988321?dopt=Abstract

    http://www.ncbi.nlm.nih.gov/pubmed/10796155?dopt=Abstract

    http://www.greenjournal.org/cgi/content/full/97/4/577

    http://www.ncbi.nlm.nih.gov/pubmed/14634571?dopt=Abstract

    http://www.ncbi.nlm.nih.gov/pubmed/15802416?dopt=Abstract

    My own view is that this kind of evidence suggests that it may be useful to investigate ginger for a possible anti-nausea substance(s). If such is found it can be standardized for dose-risk and dose-therapeutic effect relations, and also provide a potential starting point for new, more specific (and therefore safer and more effective) synthetic analogues. That is the rational process for discovering and developing new, useful drugs, as has previously been done with numerous substances found in nature.

    The “CAM” process is quite different: it assumes, for various implausible reasons, that preparations made from the whole root (in this case) are preferable to purified molecules, both in safety and effectiveness; it neglects the nearly impossible task of standardizing potencies of the several potential biologically-active molecules in the plant, given the number of varieties, the ever-changing growing conditions, and the many extraction methods; and it makes an arbitrary and therapeutically irrational distinction between “natural” and “synthetic,” always preferring the former—whereas the latter has the greater chance of being useful, for the reasons mentioned above.

    I don’t know how many readers remember a coarse talk-show host in NYC in the ’60s by the name of Joe Pyne. He was a right-wing shock-jock, kind of a precursor of Bill O’Reilly and Rush Limbaugh. At one point the anti-war crowd were wearing buttons that read “Send Joe Pyne to college.” I’ve been fantasizing a button reading “Send pec to medical school.” I’m sorry, pec; I want to like you, in the sense that I’m content to believe that you are sincere but that you are a victim of a woefully inadequate grounding in both science and in critical thinking skills, and for that I feel genuinely sorry for you.

    But you write, “A physician who knows nothing about health except which drug to prescribe, or what diagnostic and surgical technology to use, is incomplete as a health expert”—as though “which drug to prescribe” and “technology” overwhelm physiology, anatomy, biochemistry, neurobiology, immunology, hematology, histology, embryology, genetics, pathophysiology, pharmacology (which is not the same thing as “which drug to prescribe”), the natural history of disease, learning how to take histories that are useful, other interviewing techniques, physical examinations, making sense of signs and symptoms, smatterings (at least) of almost every clinical field from psychiatry to pediatrics to obstetrics to internal medicine to surgery and various surgical sub-specialties, radiology, dermatology and more, learning preventive medicine and clinical problem-solving, learning how to think about clinical research and literature, and all the rest of the enormous body of knowledge and skills that constitute becoming a physician.

    You present a broad and complex topic (“stress”) as though it were specific and simple. You readily offer truisms, written in the phony passive voice (thank you, Calli Arcale), such as “It is well known that mental states can influence physical health,” when the reality is far less sanguine. All of this betrays immaturity and a lack of sophistication.

    If you are actually a young person, perhaps of college age or not much older, I implore you to re-apply yourself to your studies and stop wasting your time here looking for reasons to make inane, contrary comments. If you are as old as you’ve represented yourself to be, it’s time to take a good, long look in the mirror and start owning up to the truth: either you didn’t really read Sagan’s “The Dragon in My Garage,” for example, or if you did you missed its point.

    KA

  19. Harriet,
    Sorry, I was writing my comment while you posted yours and didn’t notice that you had already addressed the evidence about ginger.
    KA

  20. ellazimm says:

    Sorry to put this on this thread but I wasn’t sure where else to post:

    The three feeds are not all in sync. The RSS 2.0 feed goes up through the end of Feb. The RSS 0.92 feed starts at March 4th and I forget what the Atom feed is doing.

    Anyway, my feed reader is set on RSS 2.0 and I’ve got to go to the site to see stuff published this month.

    Sorry for the interruption.

  21. ellazimm says:

    Sorry, sorry, I discovered my problem. My blog-fu is not strong today. That and a (hopefully short) bout of stupidity. Sigh. I hope the rest of the day isn’t like this.

    Carry on please.

  22. daedalus2u says:

    I suspect that the nausea of morning sickness is actually a sign of very high NO levels and that this high NO is actually beneficial to pregnancy outcomes. There is an inverse correlation with nausea levels and adverse pregnancy outcomes.

    Nitric oxide is involved in some types of nausea. Other nausea is exacerbated by placebos. Nausea is often a normal accompaniment of gastric hypermobility. The gut is nitrergic, suggesting that high NO causes both. Acute hypoxia can cause nausea. Vomiting (a not infrequent outcome of nausea) is mediated largely through smooth muscle which is largely regulated through NO.

    I speculate that the reason that very high NO levels are desirable during the first trimester is that is when most all of the differentiation is happening and when DNA replication and epigenetic programming has to have the highest fidelity. During organ differentiation is the time when a lot of epigenetic programming of those organs occurs. Many mechanisms are known to involve NO. Many organs are known to be programmed in utero including liver, heart, vasculature, endocrine system, etc. It would be beyond surprising if the most important organ, the brain were not. Some of my research involves the programming effects of NO on various organs both in utero and later. NO is an excellent antioxidant, several thousand times better than vitamin E. High NO causes high ATP via sGC allowing metabolic functions to operate well. NO blocks formation of superoxide by hemes.

    The metabolic demand in the first trimester is small. Some studies actually show reduced basal metabolic rate during the first trimester over the non-pregnant state. Expanding mitochondria and erythrocyte production is important, and both of those are directly increased by high NO levels.

    I suspect that if this high NO level is reduced by any mechanism that adverse pregnancy outcomes will increase. This increase may be quite modest and difficult to measure. It may also have quite diverse and idiosyncratic effects. It is not that the anti-emetics are causing any adverse outcomes, rather more adverse outcomes accompany a low NO state. The details of which specific adverse outcomes occur are complex and could be all over the map.

    Any treatment that reduces NO levels would be expected to have these effects. Ginger has a number of molecules that are metabolized by the cytochrome P450 system. The P450 system is regulated by NO, and is quite uncoupled, that is it produces superoxide when metabolizing compounds. A plausible mechanism by which ginger reduces nausea is by causing local oxidative stress due to activation of P450 enzymes, which pulls down the NO level and reduces the threshold for nausea. If that is the mechanism, then it would likely also reduce the threshold for adverse outcomes in pregnancy.

    I suspect there is no method that will reliably reduce nausea in pregnancy without increasing adverse outcomes in pregnancy (at least slightly). I suspect that even biofeedback and purely neurogenic methods will still increase adverse effects via decreasing NO levels. These effects would be very difficult to see, and as I see them are part of the “normal” spectrum of outcomes of pregnancy. The slight increases may not be measurable. Adult hypertension is a known consequence of “stress” in utero. Stress is a low NO state, the “adverse outcomes” can also be thought of as normal stress responses. In the “wild”, a time of high stress is not a good time to be pregnant. Ending that pregnancy in the safest way, such as via preterm birth might be one of the “normal” responses to low NO. If one carries that pregnancy to term, the infant’s physiology needs to be programmed to survive in a high stress environment. The increased adverse effects due to lowering NO in pregnancy that I am contemplating would be independent of any other direct adverse effect anti-emetics might have.

  23. apteryx says:

    Thanks to Drs. Hall and Atwood for providing links in response to Joe’s query. I see no reason to respond further to Joe, and given his rhetorical style, hope that he is not actually a practicing MD.

    Dr. Atwood writes:

    “My own view is that this kind of evidence suggests that it may be useful to investigate ginger for a possible anti-nausea substance(s). If such is found it can be standardized for dose-risk and dose-therapeutic effect relations, and also provide a potential starting point for new, more specific (and therefore safer and more effective) synthetic analogues. ”

    Therefore, how? This is not a law of nature; it’s an article of faith, touted without evidence. I picked ginger as an example, rather than another well-proven botanical such as horse chestnut, because it is also a conventional food. We seldom worry about “dose-risk relations” when we eat food, yet somehow we survive. If an isolated and patented molecule were always “safer and more effective” than plants as found in nature, then No-Doz would be safer than green tea, a capsule of pure sennoside would have fewer side effects than senna tea, and …oh, yeah… pure cocaine would be safer than chewing coca leaf. More often, I think, concentrating any one of the multiple active compounds in a plant and giving an enormous dose of that alone is a good way to increase side effects.

    Anyway, how can you claim that your potent single molecule will be BOTH safer and more effective? You are saying that the single molecule will be more bioactive in terms of desired effects yet less bioactive when it comes to causing side effects — and that this is not just occasionally true but a general rule. Can anyone come up with any supporting evidence for that? The idea that the health benefits of fruits and vegetables can be replaced by a vitamin pill has already been clearly debunked.

  24. Joe says:

    The American Cancer Society on ginger:
    http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Ginger.asp?sitearea=ETO
    “Ginger reduces nausea, according to some, but not all, controlled studies in humans. Although some clinicians warn that using ginger during pregnancy or breast-feeding (at doses that are higher than the amount eaten in foods) might cause harmful effects, there is no objective evidence of harm to the mother, fetus, or infants.”

    This is not the ringing endorsement implied by Apteryx.

    More from the ACS “Ginger may interfere with blood clotting …”

    If ginger is effective, by identifying and isolating the anti-nausea component we may be lucky and remove a component that interferes with clotting (if it exists).

  25. Joe says:

    Harriet, your link to the AAFP looks exactly right; but, for me, I get to a page that tells me the page does not exist, and invites me to search for the article. I typed-in ginger, nausea and the June, 2007 review was at the top of the list. The URL for the article looks exactly like the one you posted.

    Apteryx wrote “I picked ginger as an example, rather than another well-proven botanical such as horse chestnut …”

    http://www.mskcc.org/mskcc/html/69256.cfm
    “Horse chestnut seed is classified by the FDA as an unsafe herb.”

    Apteryx wrote “You are saying that the single molecule will be more bioactive in terms of desired effects yet less bioactive when it comes to causing side effects — and that this is not just occasionally true but a general rule. Can anyone come up with any supporting evidence for that?”

    Salicylic acid is found in some plants (e.g., meadow sweet, not in willow) and it has antipyretic and analgesic properties. However, it is very irritating to the stomach. Acetyl salicylic acid (aspirin) is more pharmacologically useful and much better tolerated. (A. Pengelly “The Constituents of Medicinal Plants” CABI, 2004 p. 18).

  26. Zetetic says:

    Yes, a specific molecule would be more bioactive than “natural” and could cause side effects. However, with a KNOWN potency (unlike the natural), the dosage could be titrated to lessen the side effect while seeking the effective dosage.

  27. daedalus2u says:

    Apteryx, it is pretty obvious that not all compounds in ginger are pharmacologically active in reducing nausea. There are at least thousands of compounds, more likely tens or hundreds of thousands. If a compound has no therapeutic effect in reducing nausea, it may still have physiological effect in causing side effects. Removing compounds that don’t reduce nausea and that do cause side effects will both increase efficacy and reduce side effects.

    Identifying those compounds and supplying them in pure form at known dosages allows the therapeutic effect to be titrated against any side effects. Something that cannot be done with materials of unknown composition with variable effects and side effects.

    Cocaine has a high potential for abuse both as pure cocaine hydrochloride and also as coca leaf. Pure cocaine hydrochloride can be used as a local anesthetic. Something that coca leaf cannot be used for.

    A dull knife is “safer” than a sharp knife. A dull knife is also a lot less useful as a tool. Sharp knives should be only used by those proficient in their use so that accidents and abuse is avoided. The same is true of purified pharmaceutically active agents.

  28. apteryx says:

    Zetetic – Anti-botanical pundits tend to assume that botanicals have only one active molecule, which presumably causes side effects as well as benefits. Yet they promise that the drug-discovery process will give us souped-up effects with reduced side effects. How is that possible? Also, above, you are assuming that there ARE significant side effects to begin with, otherwise we could hardly demand that consumers spend more money on the drug product to “lessen” them. By and large, the botanicals still allowed on our market are very safe. Some, like ginger, are foods. How likely is it that a randomly selected Big Pharma product will be safer than a food?

    To address Joe’s remarks for the benefit of other readers:

    Homemade horse chestnut products indeed are unsafe. Commercial products are made with specific techniques to remove the toxic compounds — some people seem to think there is no such thing as standardization of botanicals, but there is — and have generally minor side effects in clinical trials. There have been enough trials of horse chestnut for leg edema that it received a favorable Cochrane review. FDA has no evidence that the commercial products are dangerous in ordinary use. If they did, they would have the power under DSHEA to remove them from the market. The MSKCC site Joe linked to has the following to say:

    “Commercial products should be standardized to 50 mg of aescin and free from aesculin, a hydroxycoumarin. Studies have shown clinical efficacy in chronic venous insufficiency (7) (8) (9)…. At recommended doses no significant adverse reactions are reported.”

    This is not the dire warning implied by Joe.

    Acetylsalicylic acid (aspirin) is easier on the stomach than purified salicylic acid was, although aspirin still kills thousands of people annually. Willow bark contains salicin in relatively low doses. It is not clear whether the low-dose salicin in willow bark tea is more or less irritating than high-dose aspirin. Anyway, if the aspirin is safer, that would be one instance for which that was true. I was asking for support for the general claim that if you select a random botanical and make a concentrated drug from one of its active molecules, that drug will be “safer” than the botanical – which is ludicrous on the face of it. It is true for digitalis. It is not true for cranberry juice.

  29. apteryx says:

    Daedalus -
    In other words, the potent pill with its delicate balance of benefits and toxicities can only be prescribed by an MD, and therefore received only by someone who can shell out $100 or so for the office visit – plus maybe more money for office visits for more prescriptions to deal with the side effects. With botanicals, you can sometimes go to the grocery store, or your own backyard, and get perhaps weaker effects for $2.

    Again, why do you fret so about the “side effects” of ginger? Do you have any reason to think there ARE any? Has anyone in recorded history ever dropped dead from eating stir-fried ginger?

  30. daedalus2u says:

    There are more reasons to think there are side effects from ginger when used as a drug than there are reasons to think there are no side effects when using ginger as a drug. The only way to determine if there actually are side effects of using ginger or the pharmacologically active compounds in ginger is to test them. Until they are tested, whether they do have side effects or do not have side effects is unknown.

    Humans did not evolve in symbiosis with ginger. The compounds in ginger are xenobiotic as far as human physiology is concerned. The ginger plant was not intelligently designed so as to provide an anti-nausea drug for humans. The ginger plant evolved to have these compounds in it for its own reasons, not to provide medicinal effects to humans. Many compounds in plants are there to deter predation by herbivores.

    Some compounds that are teratogens have no or only minor adverse effects in adults. Until the compounds in ginger have been tested whether they are teratogens at what doses remains unknown.

    Alcohol has been used as a food for millennia. It is now well known to be a teratogen.

  31. apteryx says:

    All I can offer for ginger is: A, one rat study of teratogenicity (not finding any); B, no increase in birth defects in any of several human trials; and C, the fact that in parts of India pregnant women make a point of eating a lot of ginger, and they reproduce successfully enough to have one hell of a population problem. What do you want to hear? You say that only formal trials mean anything, then you don’t seem interested in the results of the trials that have been published. If Santa Claus gave me a couple hundred million to do a study with thousands of pregnant women, would you accept the results of that study, or would you carp that it was unethical to “put their babies at risk by letting them consume a botanical”?

    I suppose humans could be said not to have “evolved in symbiosis” with any food plants not native to Africa, although humans have been in Australia, via Asia, for 50,000 years. But somehow I don’t think you would be less fearful of African wild plant foods than of the European cultivars that we’ve used for less than two millennia. You could make the same claim above about any food plant whatsoever. I don’t like cauliflower; well, it’s got icky-tasting defensive secondary metabolites in it, maybe it’s a teratogen. Maybe they should get that stuff off the market “until it’s tested.” Should pregnant women eat nothing but white flour and meat (aka the Bland Cancer-Promoting Diet)? What about the large majority of the population who are not pregnant? Can they take it that a plant is safe enough for medicinal use, if hundreds of millions of people have eaten it for dinner?

    I say this in a friendly spirit: Piffle.

  32. daedalus2u says:

    I don’t say that only formal trials mean something.

    When there is no general understanding for the physiological basis behind the nausea of early pregnancy, and when there is an inverse correlation between nausea in pregnancy and adverse pregnancy outcomes, I think it is presumptuous to assume that treatments that do away with nausea have no side effects. The physiology that causes the nausea may have a beneficial role all by itself. All women may not react the same way. All fetuses may not react the same way. All ginger may not be equal.

    There may be changes that are real, yet may be too subtle to measure in any particular individual. For example adults exposed to nutritional deprivation in utero have more health problems as adults.

    http://jp.physoc.org/cgi/content/full/565/1/27

    http://www.pnas.org/cgi/content/full/104/31/12796

    Some of these effects are subtle and may not show up until middle age. Did someone with the metabolic syndrome get it because of exposure in utero or because they didn’t exercise or because their mother ate ginger as an anti-emetic?

    I am not making a claim; you are making the claim that there are no adverse effects from eating pharmacological doses of ginger. At some dose ginger does have side effects. Ginger does have an LD50.

    When purified compounds are used, the metabolism of them is simpler than the metabolism of those compounds plus thousands of others. It is easier to look for side effects with a single compound than for a complex (and variable) mixture of thousands of compounds.

    I don’t know if ginger has adverse effects during pregnancy. If “everyone” in India eats ginger during their pregnancy, perhaps they are all immune, or perhaps if they didn’t eat so much ginger over historic time we would now be speaking Hindi because Indians would have industrialized first and conquered the world instead of Europeans. Maybe ginger does cause problems during pregnancy but perhaps ginger is also good treatment for intestinal parasites native to India and if you have intestinal parasites getting rid of them with ginger is worth the side effects that ginger has.

  33. “You are saying that the single molecule will be more bioactive in terms of desired effects yet less bioactive when it comes to causing side effects — and that this is not just occasionally true but a general rule. Can anyone come up with any supporting evidence for that?”

    Yes, it’s a general rule, and yes, there is plenty of supporting evidence. Others have already begun to explain, but the points are these: a single molecule lacks the biological (“side”) effects of the many other molecules that exist in a mixture; a known dose of a single molecule provides a more predictable biological response—both desired and undesired—than an unknown or widely-varying dose of that same molecule (as is typically found in a plant or plant extract); and chemical alterations of a single molecule can (and have, many, many times) result in new molecules that are either more specific for a desired biological effect than was their precursor (and thus as effective at a lower dose, hence reducing undesired effects) or that have lower incidences of undesired effects, or both.

    That “formulation” (ouch!) is the basis for modern pharmaceutical development. Please don’t confuse what’s wrong with “BigPharm”—shameless advertising, COIs involved in sponsoring trials, concealing of unflattering information, which we bloggers don’t like any better than you—with what’s right with it: pharmaceutical R&D and manufacturing, ie, the science and technology. There are so many examples that it would (and does) take whole textbooks to illustrate them, but it’s easy to find several that are relevant to material on SBM.

    Consider an example that you cited: Google “cocaine” and “local anesthetics” and you’ll quickly find an historical timeline leading from the intriguing but not very useful effects, in the medicinal sense, of coca leaf, to cocaine itself 150 years ago, which is an excellent local anesthetic (it was how local anesthesia was discovered) but has other effects that are undesirable, to the first synthetic analogue, procaine (Novocaine, ca. 1910), which lacked those undesirable effects, to lidocaine (ca. 1940), the first really good synthetic LA (it has a more rapid onset than procaine, gives a more intense nerve block, and lasts longer), to procainamide, bupivicaine, prilocaine, mepivicaine, ropivicaine, and other synthetic derivatives, each of which has useful distinguishing properties.

    Some are longer acting, some are shorter acting, some have less effect on the electrical activity of the heart, which makes them safer for the large doses used in major nerve blocks, others have specific effects on the heart that makes them useful as anti-arrhythmics(procainamide), some have greater or lesser effects on the brain; the entire class of “amide” local anesthetics, of which lidocaine was the first, is less allergenic than its “ester” precursors (of which cocaine is one); and more.

    All LAs, beginning with cocaine, have similar tertiary structures: a lipophilic end (typically an aromatic ring), a hydrocarbon chain (no more than 2-3 carbons, typically), and a hydrophilic end. Altering any of these regions changes biologic effects, and after much experience such “structure-activity” relationships both help us learn about how things work and allow pharmacologists to make educated guesses about what new alterations might be useful.

    This sort of process has been successfully used countless times. Other examples relevant to SBM posts include HMG-CoA reductase inhibitors (“statins”), originally isolated from microorganisms much more recently (ca. 1970), with synthetic derivatives that have varied widely enough in adverse effects to suggest that it will be possible to fashion new ones that have extremely low risks but maintain the desired effect. I won’t get into the statin argument here except to make a point that may not have been made before: as drugs go, these are quite new and have a huge upside potential for improvement.

    Another example relevant to SBM is cinchona bark, from which quinine was found to be the active antimalarial ingredient, which itself led to the synthesis of the useful drugs quinidine and mefloquine. Artemisinin, an antimalarial from the Chinese artemisia tree whose specific identity and proof of effectiveness was accomplished only 35 years ago, even though it had been part of herbal fever remedies for hundreds of years, is also now in the process of being altered for useful analogues.

    A few readers probably have asthma. Let’s look at one of their staple treatments from the opposite direction of time and innovation: albuterol is a synthetic “beta-2 agonist.” That means that it stimulates beta-2 adrenergic receptors, which mainly causes bronchodilation (useful for asthma) and uterine relaxation. If an asthmatic who isn’t pregnant inhales albuterol, the main effect is desirable and the side effects are minimal. A few years ago the best beta receptor agonist, isoproterenol (also synthetic), was not specific to receptor types 1 or 2. Thus if an asthmatic came to an emergency room needing treatment, he was likely to get a drug that worked but caused unpleasant heart-racing as a side effect, or perhaps he was denied that drug because it would have been too dangerous if he also had heart disease.

    A few years before that, the only choice for a beta-adrenergic agent would have been the naturally-occurring epinephrine (adrenaline), which is not only non-selective between beta-1 and 2 receptors, but also between alpha and beta receptors. Thus dangerously high blood pressures and several other side effects would have been added to those previously mentioned.

    In theory it could have been even worse in the old days, if cow adrenal glands—with norepinephrine, a very potent natural alpha agonist, several kinds of steroid hormones, and numerous other molecules that our bodies would probably not much like—had been ground up and used as either inhaled or injectable medicines. As far as I know that was never done, but it would be the obvious analogy to the “CAM” preference for whole plants or parts of plants—except, of course, that if such a preparation were taken by the oral route it would be relatively innocuous, and the adrenergic molecules themselves would not be sufficiently absorbed to have any effect, useful or otherwise. I realize I’m wandering a bit here.

    Everyone can think of other classes of drugs that have gone through the stages of native source–extraction–purification–standardization of potency and dosing–synthesis of analogues, resulting in predictable, useful improvements in desired and undesired effects at virtually each stage. Two more examples are antibiotics and narcotics.

  34. Wallace Sampson says:

    Thanks to Joe, Daedalus, and Katwood, I am receiving an ecellent Board xam review in pharmacology, and also receiving points in my ongoing arguments with a certain family member as to “why” I am on this blog.

    Returning to the titled subject, “CAM” teaching in medical schools, I can offer the following, which I hope can add insight into the questions as to “why” we have coe to this.

    I have two or three articles on this if one has time and the interest to read them. One on The Need for reform in Teaching of “CAM” in medical schools is in Academic Medicine, 2000-2002 – see Pubmed listing. (I am now repeating what I placed in a prior entry.) I implied that we were then on an asceding curve of sectarian med entry into medical schools. Of the then (1995-7) 57 or so courses in 125 US med schools only 4 or 5 taught subjects from scientific, analytical view. Since then, 2 of them are gone with the retirement of their teachers. One newer one appeared (U Brit. Col.) in Canada.

    I reviewed the content of many of the courses through questionnaires, web sites, and requested outlines. The questionnaire replies were sometimes caustic and cynical, the course heads (joke?) having sniffed out my “bias.” But most were straightforward. Fifty two never entertained presenting scientific arguments opposing efficacy/use, and none invited a skeptical presentation.

    The editors did not want to publish the article – a subject for longer exposition – they objected to the time delay, the “orientation” and so forth. It made them uncomfortable. And much -including the caustic comments – was redlined. But talk about an anechoic response…the anti-echo came back with new foundations with more and diferent funding agendas, providing fertilizer ($$$$) for the courses David Gorski described. It seemed that the only peole who read it or were affected by it were proponents, who felt it as a whip on their behinds so to run even faster.

    The other two articles are on the history of the “CAM” development in No. America and Europe. It looked to me like the pseudoscience interest rose and fell over time in a cyclic fashion, like so many other social phenomena, but with separate waves of differing methods out of phase.

    The 3rd one was on the influence of post-modernism and cultural relativism (CR) on preparing the soil for the present growth. Here seemed to be the missing link that turned the heads of the academics and a significant percentage of mystical-bending practitioners, and spurred interest the splay of non-professionals and quasi-professionals whose ads one sees in small weekly newspapers and in Yellow Pages.

    CR as has been discussed, creates a content equity between scientific and pseudo-scientific systems. CR’s association with racial equality and international commercialism, environmental conservation, and other social goods and artifacts of modern living, benefits from use of common language and a commonality of thought about dangers and misuse of science (radiation, animal experimentation, synthetic chemicals and drugs. And, professionalism and intellectual know-it-allism) So scientific medicine becomes a stand-in enemy for unhappy and somatiforming souls, whose internally generated conflicts can be comfortably externalized and then written about, meeting-about, and scolded through faculty meetings.
    Political/academic correctness takes care of the rest.

    But how about them funders? The NCCAM is the biggest of course, and combined with service departments (Army, Navy, Defense Dept. and now USAF) has exceeded $1 billion.

    The second largest, Bravewell, is the main private force behind development of courses and training programs. They have gathered 35 + med schools for teaching courses and a lesser number for postgraduate training in “CAM.” The NCCAM appropriated something like $10 million for fifteen med schools PG programs. This is for teaching practitioners, no less, not just teching students about “CAM.”

  35. Wallace Sampson says:

    [Sorry, the post went off prematurely...]

    The second article above on the history is in Sci Rev Altern Med, and the third, “Postmodern Medicine” is also. That journal is not abstracted on Medline. When the publisher updates the web site (SRAM.org) some articles will be there.

    Looks like we will be covering some previous ground, but there is enough new every 4 years to do so – maybe evry year at this rate of change.

    WS

  36. apteryx says:

    Dr. Atwood -

    I have seen someone (can’t remember who) make the following argument: Suppose you were to go into a pharmacy blindfolded, pick either one herbal dietary supplement or one prescription drug derived from a natural product off the shelf at random, then take the whole bottle at once. Which would be more likely to severely harm or kill you? No question, it would be the drug.

    The drugs you mention are indeed improvements over the natural products from which they are derived. Artemisia annua tea is a fairly effective treatment for malaria, but concentrated derivatives of artemisinin (which is only one of several active compounds) are even better, and given the degree of misery malaria causes, patients who can afford them will prefer them. But the more potent product is not always better. There is a balance between potency, cost, and side effects, and it does not make sense to attack every symptom with the biggest possible hammer no matter what. Also, some botanicals cannot be turned into single-compound drugs without losing efficacy. If there were only one molecule in horse chestnut that affected leg edema, or only one molecule in hawthorn that improved heart function, some drug company would by now have sifted it out, slightly altered and patented it, and be doing Phase III trials. These botanicals have whole suites of active ingredients, and patients will gain more benefit from multicomponent products.

    To return, as Dr. Sampson has done, to the original theme — these are not controversial statements among people aware of the state of research on botanicals. Traditional med schools have been cranking out doctors who believe, and instruct patients, that plants are probably harmful but never helpful unless they both can be and have been made into drugs. These days, many patients are too well informed to accept such blanket claims. If I come into your office and suggest trying ginger rather than the side-effect-heavy drug you might prescribe for my motion sickness, and you go off on a tirade suggesting, like Joe above, that I may belong to a “pseudomedical cult” or, like Daedalus above, that consumers of non-European cuisines may be somehow defective — well, next time I have a minor condition to deal with, I will say the heck with you and look for an herbalist. To put it in economic terms, since medicine is a lucrative industry these days: You will lose business. If you want to keep me as a patient, you don’t need to recommend traditional medicines, but if you want to express strong opinions on the subject, you had better show that you have seen as much of the relevant research as I have.

  37. “Suppose you were to go into a pharmacy blindfolded, pick either one herbal dietary supplement or one prescription drug derived from a natural product off the shelf at random, then take the whole bottle at once. Which would be more likely to severely harm or kill you? No question, it would be the drug.”

    I agree, but the reason is a simple one: most “herbal dietary supplements” have much lower doses of biologically-active substances, whether helpful or harmful, than do prescription drugs. Don’t we agree that if the same biologically-active molecule is present in the same dose in a pharmaceutically-manufactured pill or in a plant extract, that its biological effect must be the same? You imply, later in your comment, that the recommended doses (if that’s what you mean by “potency”) for pharmaceuticals are too high. That’s possible, but seems unlikely in light of their having been determined by dose-response trials. An alternative explanation is that consumers’ perceptions of the effects of most “supplements” are not based on specific biological activity.

    Regarding the “multicomponent” argument: do you have real evidence of this? I must admit that I’ve never been interested enough in the woo-ery of herbalism (it’s so prosaic compared to the really magical stuff) to investigate this claim, although one hears it all the time. It’s not entirely implausible, in a way: many biologically-active molecules in plants, including some that have become medicines, appear to have evolved as defenses against predators (mainly insects). It is true that there can be more than one poison in a plant, perhaps each having conferred a selective advantage against the same species or similar species of insects. Perhaps the various poisons have additive or even synergistic effects on particular insects. If so, this ought to be known to legitimate botanists and entomologists. Any out there?

    Yet even if that is true, it doesn’t follow that additive or synergistic medicinal effects must exist for substances found in plants that have useful medicinal properties for humans. Typical claims of that sort by “CAM” types betray their naivete about nature. Consider the following statement by the former Chief Medical Officer at the Southwest College of Naturopathic Medicine. It suggests “intelligent design” or some similar, comforting but childish notion that nature is our Mary Poppins:

    “What’s nice about plant or herbal medicines
    is that because they are derived from the whole
    plant they are considerably less toxic to the
    body. The plant medicine has evolved to work
    in harmony with the normal body processes
    rather than taking over its function as many
    drug therapies do. Because of this herbal medicines
    may be taken for longer periods of time
    without the side effects so often experienced
    with drugs.” ( http://web.archive.org/web/20050825191221/http://www.scnm.edu/news/uploads/ms.pdf )

    Excuse me, but equipotent doses are equipotent, no matter what the packaging. And there is no reason to think that “plant medicine has evolved to work in harmony with the normal (human!) bodily processes.” That’s just wishful thinking.

    Again, I don’t know that there aren’t examples of medicinal plants containing more than one molecule useful for the same human problem. I am quite sure, however, that there is no compelling reason in biology to think that this should be the norm, or even common.

  38. apteryx says:

    I’m afraid addressing all the mistaken ideas in the above message would take a very lengthy response, which as Dr. Sampson would note, would be a distraction from the major thread. However, if your med school told you anything about botanicals, it should have told you that it is VERY common for plants to contain whole suites of structurally similar secondary metabolites, which may serve many purposes other than “poisons” – of course, what is a “poison” to a bacterium may be beneficial for us! Sure, some consumers assume every plant’s virtues derive from synergistic or additive effects, and that is not always true. But if you get a certain result in a bioassay or clinical trial from a whole extract, then can’t find any single molecule that has the same bioactivity profile when given in the same (relatively small) amount as was present in the extract, the only mechanist conclusion possible has to be that there is more than one active molecule present.

    To return to the proper theme, your med school should also have taught you not to label patients who understand that with words like “woo-ery,” “naivete,” and “childish.” You admit that you have little knowledge of botany or the irrelevant science of entomology; I hope you do not display open contempt for non-MD patients if their greater knowledge of botany causes them to disagree with some opinion you hold dear.

  39. daedalus2u says:

    I don’t know how you get from my examples the possible notion that I suggested that consumers of non-European cuisine are in any way “defective”.

    Tobacco has been consumed for centuries. Is tobacco without side effects? Are people who choose to consume tobacco somehow “defective”? Addicted yes, addicted to an herb.

    The same is true with salt. Salt has been consumed by humans for forever. It is actually a necessary dietary component. Is consumption of salt without side effects? Consuming an entire retail container of salt (26 oz or 740 grams) would likely be fatal. In rats the LD50 is 3 g/kg.

    The fact is, that membership of a material in a group called “herbs” or “chemicals” or “foods” or “drugs” or “pharmaceuticals”, or “white powders” or “sold in containers of lethal quantities” tells us nothing about the safety or dangerousness of the material. Salt is a member of every one of those groups.

  40. apteryx says:

    Well, Daedalus, when I observed that many of the 2.5 billion Indians and Chinese eat ginger regularly, and yet there are 2.5 billion of them, you responded as follows:

    “If “everyone” in India eats ginger during their pregnancy, perhaps they are all immune, or perhaps if they didn’t eat so much ginger over historic time we would now be speaking Hindi because Indians would have industrialized first and conquered the world instead of Europeans. ”

    If you suggest in utero or in vivo exposure to ginger could possibly have prevented Indians from industrializing “first,” you imply that ginger consumption could possibly create some unspecified biological condition that prevented them from being good productive capitalists and conquistadors. But you probably can’t imagine what condition, any more than I can. Since, excluding diseases caused by known deficiencies and pathogens, Asians are not known for being physically feeble and debilitated, I assume that you were implying ginger could have somehow mysteriously affected Indians’ mental faculties. (Apparently for the better, if an inability to rape and pillage the rest of the world is the only “symptom.”)

    A more plausible explanation of why Indians didn’t industrialize first is that (a) they didn’t have large accessible coal reserves, which is not causally correlated with consumption of spicy foods, and (b) they live in the tropics, an area historically not conducive to sweatshop labor — which is. Do you maybe want to back off a bit from your earlier comments?

    Announcing that every substance is toxic in excess is not a valuable revelation. Practically everyone knows that, and it tells us nothing about what substances are toxic under normal circumstances. One of those things that med students really ought to be learning [note casual segue back to original topic] is that when people from India and China start eating the Western diet, their health worsens. Instead of drumming up fear of spicy vegetables, perhaps they should start trying to quantify the toxic dose of grain-fed red meat.

  41. daedalus2u says:

    There are many more plausible reasons that Indians didn’t conquer the world than because they ate too much ginger. I threw that out there as an attempt to be humorous, but also to make the point that even though things have been used for a long time doesn’t mean they are safe.

    The major traditional medicine of India is Ayurveda which uses heavy metals (mercury, arsenic and lead) in quantities that exceed levels now considered to be safe.

    http://jama.ama-assn.org/cgi/content/abstract/292/23/2868

    http://www.indianexpress.com/res/web/pIe/full_story.php?content_id=71247&pn=0

    The anecdotes of safe and beneficial use of Ayurveda go as far back as the anecdotes of the safe and beneficial use of ginger (that would be for all of recorded history in India).

    I am not trying to drum up fear of ginger, but rather an absence of ignorance of the pro and con effects of ginger. The only way to actually know something is to actually measure it. The Indian practices of Ayurveda reportedly were dictated by one of their gods. Not a theoretical basis that is subject to analysis.

    Should Ayurveda be taught in medical school? Should it be taught before or after the section on heavy metal poisoning and how to treat it?

  42. Joe says:

    As for the herbalist claims that herb components work together to provide some increased benefit (additive, or synergistic), the opposite can also be true- the herb can contain poisons that make the desired active-ingredient irrelevant until purified. Apteryx knows this as s/he reported “Homemade horse chestnut products indeed are unsafe. Commercial products are made with specific techniques to remove the toxic compounds” BTW, Apteryx also noted “Commercial products should be standardized to 50 mg of aescin and free from aesculin, a hydroxycoumarin.” There’s that word “should” which does not guarantee they “are.”

    Going back to whether herbs have components that work together. Artemisia annua has at least seven antimalarial compounds; but artemisinin is 1,000 times more potent than the next best (“Traditional Medicinal Plants and Malaria” M. Willocox, et al Eds. (CRC Press, 2004)). In a related note concerning herbal medicine, more than 100 “antimalarial” Chinese herbs were screened and only Artemesia had useful activity http://www.ncbi.nlm.nih.gov/pubmed/16722826?ordinalpos=21&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum .

    There is also the example of foxglove. It provides at least two drugs (digoxin and digitoxin) with similar action; but very different pharmacological profiles. Offhand, I find that “Hospitalized elderly patients taking digitoxin had a lower rate of toxicity than those taking digoxin.” http://www.medscape.com/viewarticle/410488

  43. Joe says:

    Apteryx wrote “But if you get a certain result in a bioassay or clinical trial from a whole extract, then can’t find any single molecule that has the same bioactivity profile when given in the same (relatively small) amount as was present in the extract, the only mechanist conclusion possible has to be that there is more than one active molecule present.”

    We figured that out many decades ago.

    Apteryx wrote “I hope you do not display open contempt for non-MD patients if their greater knowledge of botany causes them to disagree with some opinion you hold dear.”

    I think we have been through this. A proper response would be for the doctor to look for, and evaluate, the clinical evidence. Botanists, in general, do not know how to do that. The late Varro Tyler was the Eli Lilly Distinguished Professor of Pharmacognosy at Purdue University. He often lumped-together the good, the bad and the ugly of clinical trials to support herbalist claims.

  44. Harriet Hall says:

    Herbalists frequently claim herbs are superior because of some synergistic effect of their components. Do any of you know of examples of “whole” herbal medicines that were tested against the isolated active ingredient(s) and found to be superior? All the tests I know of showed that they were equal or worse.

  45. Joe says:

    Harriet wrote “Herbalists frequently claim herbs are superior because of some synergistic effect of their components. Do any of you know of examples of “whole” herbal medicines that were tested against the isolated active ingredient(s) and found to be superior?”

    In a word: no, I do not.

  46. “your med school should also have taught you not to label patients who understand that with words like “woo-ery,” “naivete,” and “childish.” ”

    apteryx, you misconstrued what I wrote, possibly because I did not make myself clear. By “woo-ery,” I was referring to the woo aspects of herbalism, which does not mean that there are not non-woo aspects, namely, investigating folk uses to find useful medicinal substances in plants—as I thought I had made clear from previous examples. By “woo-ery” I was referring to ideas such as those in the quotation from the naturopath, which are childish, naive, and do not reflect an understanding of anything. I was not charging you or any particular, hypothetical patient with similar notions.

    I’m sure you can also appreciate that some of the critical, uncompromising language used on this blog is not the sort that most MDs would throw at a patient who has approached us in good faith, however much we may disagree with his or her point of view. Professionalism in medicine, as in any other “helping” profession, is more compassionate and subtle than that.

    Yes, it’s plausible to “get a certain result in a bioassay or clinical trial from a whole extract, [without] any single molecule that has the same bioactivity profile when given in the same (relatively small) amount as was present in the extract.” And yes, if that were common it would make herbalism more intriguing to science-based MDs. But show us examples, please. That’s the big question, so far unanswered, at least in this thread. Joe mentioned Varro Tyler, one of the few legitimate academics in the field, who did not agree with it (see “tenet #3″ here: http://www.quackwatch.org/01QuackeryRelatedTopics/paraherbalism.html ).

    Entomology, by the way, is far from irrelevant to that very question. If widespread synergy of bio-active molecules in plants really exists, it’s likely that it will have already been discovered by entomologists and/or botanists (readers: help us out here, please). If so, even if their discoveries have only to do with substances poisonous to insects, it would provide a theoretical boost to the synergy claim for medicinal properties—even though the latter are fortuitous, existing only because biochemistry itself is similar throughout the living world. In the case of plants and insects, the phenomena are based on more than that: selection pressures imposed by each on the other over hundreds of millions of years.

    KA

  47. apteryx says:

    There are quite a few plants whose activity has been found to split into multiple fractions in bioassays, or to diminish after fractionation. I can’t list them all off the top of my head. Berberine-containing plants, which also have a compound that disables the bacterial MDR pump, making the berberine many times more effective.

    http://www.ncbi.nlm.nih.gov/pubmed/10677479?ordinalpos=29&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    There have been several studies on green tea catechins, showing that while EGCG is the only one that’s very potent directly (e.g., against cancer), the presence of related compounds boosts its activity. Here are the only abstracts I can scrounge up right now.

    http://www.ncbi.nlm.nih.gov/pubmed/15802789?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    http://www.ncbi.nlm.nih.gov/pubmed/11064004?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    Both flavonoids and procyanidins are relevant to hawthorn’s cardiovascular benefits. No, researchers have not done separate failed clinical trials with every single one of those compounds – that would be impossible as well as foolish – but they have done lab studies showing that different groups of compounds contribute to bioactivity. Animal studies suggest that both rutin and hyperforin are necessary for St. John’s wort to be active. Ginseng has dozens of ginsenosides having different activities in lab studies. The average plant has hundreds of secondary metabolites, often in groups of closely related compounds. It costs the plant something, metabolically, to make twenty saponins or alkaloids rather than just one. I think any botanist or entomologist would agree that there has to be some selective advantage to doing so.

    I would not take health advice from a botanist either [unless it was Jim Duke!] although that would be better than taking it from an entomologist. Varro Tyler was a pharmacologist, not a botanist, and he was considered by herbalists to be very conservative. But where scientific studies supported herbs, he was willing to acknowledge the facts. He deserves credit for that, not insult.

  48. Joe says:

    apteryx wrote “There are quite a few plants whose activity has been found to split into multiple fractions in bioassays, or to diminish after fractionation.”

    I think we have agreed that this can happen, if it were a general principle, we would know it. Also, we know how to recombine fractions to home-in on the best activity. To the extent that an herb has activity, it is a contaminated drug. Those contaminants vary according to where and when you harvest the herb.

    apteryx wrote “Varro Tyler was a pharmacologist …”

    No, his field was pharmacognosy, may I politely suggest that you look it up.

  49. Harriet Hall says:

    I’m sure some herbal remedies do contain more than one active ingredient. That is not what is being claimed by some herbalists – they are claiming a synergism where the joint effect is greater than the added effect of the individual components. Whatever the active components, the remedies will always contain other, inactive components, and these might be either useless or counterproductive, harmless or harmful.

    As a general principle, if an effective herbal remedy is found, its safety and effectiveness are likely to be improved by purification and isolation of active components. Aspirin is preferable to willow tree bark and digitalis to foxglove. Some herbalists try to tell us the opposite is true, but the evidence doesn’t support them.

  50. apteryx says:

    Then perhaps Big Pharma would do us the favor of filling in a few gaps in their armamentarium by manufacturing:
    - a single compound derived from hawthorn to alleviate symptoms of heart failure while reducing, rather than increasing, the risk of arrhythmias
    - a single hepatoprotective compound derived from milk thistle (MDs who do not wish to risk malpractice suits already treat amanita poisoning with silymarin, which is a standardized mixture of four active molecules – you can find reports on PubMed)
    - a single compound derived from horse chestnut to treat chronic venous insufficiency
    - a single compound derived from gotu kola to speed wound healing and treat microangiopathy, and
    - a single compound derived from elderberry to fight flu.
    And it would be nice if in every case, their molecule was significantly more potent without having serious side effects, or equally potent without any more side effects or greatly increased cost. If it’s that easy to find “THE” active ingredient and concentrate it without losing benefits or creating hazards, there’s a lot of money to be made; why don’t they get cracking?

    I said I wasn’t going to waste further time responding to Joe’s posts, but for the benefit of any readers who do not know what pharmacognosy is, it is the pharmacological study of botanicals or other natural products. It used to focus on whole plants, but now spends most of its time pursuing pharmacological studies of active molecules of interest. It is a subdiscipline of pharmacy, not botany. The late Dr. Tyler studied pharmacy at the University of Nebraska, was in 1953 the first person to receive a Ph.D. in pharmacy from the University of Connecticut, and spent most of his career at Purdue’s “Department of Pharmacy and Pharmacal Sciences,” of which he was for some years the dean. Tyler took a conservative position, for example arguing that willow bark could not work as an analgesic (despite its use on three continents) because the dose of pure salicin was small relative to the maximum permitted dose of aspirin. (This was before any clinical trial of willow bark had been done.) He had very little if any interest in human use data; he was a pure scientist. Sadly, sometimes the science supports traditional practices.

  51. Harriet Hall says:

    “there’s a lot of money to be made; why don’t they get cracking?”

    Why don’t you ask that of someone in the industry who is in the know? Perhaps it is because they have looked at these plants and decided that the evidence isn’t promising enough to make it a good business proposition.

    Big Pharma does develop drugs from plants and folk remedies. Why do you think they developed aspirin and Digitalis? How do you think they choose which plants to investigate?

    A drug company recently tried to develop a pharmaceutical version of Hoodia, but they gave up when they were unable to separate out a hepatotoxic component.

  52. apteryx says:

    How do you know that hepatotoxicity was the real problem? AFAIK, no published data support that. There is no evidence that the plant as traditionally used is hepatotoxic, so if the active molecule when concentrated were hepatotoxic, it might be a case where the drug model reduced safety. (IMHO, the real problem with Hoodia products is that most of them are fake.)

    If the drug companies think the “evidence isn’t promising enough” to justify investigation of those botanical uses I mentioned – most supported by multiple clinical trials and multiple animal studies and, in some, in vitro explorations of mechanism – even though none of their magic-bullet drugs can offer the same bioactivity profiles, then it is entirely rational for consumers who could benefit from those bioactivities to go on using the plants as people have done for millennia. You can comfort yourself with the belief that each has only one active molecule and that putting that molecule in a pill would be even better. Since there is no such pill, consumers will reasonably conclude that some benefit from herbs is better than zero benefit from Big Pharma.

  53. Joe says:

    Apteryx wrote “there’s a lot of money to be made; why don’t they get cracking?”

    The usual rule about rhetorical questions is: the one who poses the question must know the answer. Please don’t keep us in suspense any longer.

  54. David J Kroll says:

    A colleague suggested that I come by to this discussion because I have spent much of my 15 yrs of independent research on natural products and herbal medicine. Apteryx does indeed seem to know a lot about my field although I’d be happy to help tone things down and add some clarity as I feel I am a stakeholder in natural products research in prescription medicine as well as in the more intellectually-accessible end of the spectrum of so-called complementary and alternative medicine – in fact, some natural products researchers are a bit miffed that their decades of legitimate work has been co-opted by purveyors of fraudulent and deceptive CAM modalities at the other ends of the spectrum.

    It may interest apteryx that I had the bittersweet honor of stepping in for Varro Tyler at a symposium held in 2001 a month after his untimely death and that my current research is actually on pure components in milk thistle (just do a PubMed search for me; however, I study their anticancer action rather than their hepatoprotective action). I am simply fascinated by the promise of herbal mixtures and their components as a source of novel chemistries that have allowed us to find new mechanisms of action to treat diseases.

    Given my background, I have never really viewed this area with the degree of conflict or confrontation evident in this comment thread. Indeed, there are a few limited cases where synergy among herbal components might support the superior action of a whole herb – my favorite case is the work of Frank Stermitz at CSU in the PNAS report cited by apteryx above. (In this case, the synergy is more accurately defined as “potentiation” since the antimicrobial efficacy of berberine is enhanced by the presence of the S. aureus NorA efflux pump inhibitor, 5-methoxyhydnocarpin – this compound has no intrinsic antimicrobial activity so the effect can be described by the analogy of 1 + 0 = 3.)

    I’ve also been involved in several NIH/NCI-funded projects over the last six years where my pharmacognosy and med chem colleagues have fractionated plant extracts that we have then tested for in vitro cytotoxic activity against human cancer cell lines. I’m sorry to say that out of ~4,000 extracts with which my lab has worked, we have yet to find a single case where synergy might be present. In the vast majority of cases, fractionation of plant extracts leads to an enrichment of cytotoxic activity (not a loss as might be expected if there were synergistic components) that can then be narrowed down to a single pure compound or related pure compounds. At the very best, we have seen nothing more than additive action among compounds where more than one was present in the extract.

    A common herbalist stance is that whole plants have fewer side effects than pure compounds because the plant contains other compounds that offset the side effects of the active constituent. Despite my willingness to consider this claim and a search of the scientific literature, there is unfortunately no evidence I can identify to support this claim.

    I can certainly identify with apteryx’s enthusiasm for wanting drug companies to isolate and market the pure compounds from herbal products that have some reported potential for biological activity. In fact, they already do but mostly as semi-synthetic analogs of the naturally-occurring compounds to overcome metabolism and solubility issues (and the patentability issues detailed below). We are trying to do that now with milk thistle compounds but the reality is that the pure, naturally-occurring compounds cannot be patented and lack of a protected IP position provides no financial incentive for the average $800 million investment required to bring a drug to market in the US. Taxol, the anticancer drug whose structure was solved by one of my current senior colleagues, is a special story of a natural compound that made it to the prescription drug market because the process to synthesize it from a renewable resource was patented, not the molecule itself.

    Although 25% of our current prescription drugs can be traced to molecules from natural sources, corporate investment in natural products drug discovery has diminished leaving much of the work to government-funded academic researchers. (Of course, drug companies might be happy to license a novel natural product derivative if you had a clear IP position and significant preclinical and early clinical data supporting safety and efficacy). Each of the projects described above by apteryx would take several, R01-sized NIH grants to accomplish. As a scientist with the training and willingness to investigate these questions, I can only hope that enough interest (i.e., funding) remains in the promise of this field for such questions to be addressed.

  55. Harriet Hall says:

    “it is entirely rational for consumers who could benefit from those bioactivities to go on using the plants as people have done for millennia”

    It is rational to some extent. It depends on one’s risk-taking propensities. Because of the DSHEA, I can’t trust the purity and dosage of what’s being sold. I keep reading about contaminants and inconsistent dosages.

    And I reject the argument that a plant-based remedy is safe just because people have used it for centuries without noticing any problems. No one was keeping statistics during those centuries. Think of HRT (hormone replacement therapy). It was used for decades by huge numbers of women before the Women’s Health Initiative finally convinced us it did more harm than good. One of those “benign” herbal remedies might just turn out to be fatal for the occasional patient; we just don’t know.

    Effective herbal remedies are drugs just as much as prescription drugs are. I would hesitate to take a prescription drug that had not been extensively tested. I prefer not to use new prescription drugs until there has been time for post-marketing surveillance to pick up unexpected problems. I think the testing for most herbal remedies has generally been inferior to the testing for prescription drugs.

  56. apteryx says:

    Dr. Kroll -
    Thanks for your very interesting remarks! I think that you are more likely to find single compounds effective in a cytotoxicity assay. That’s a very simple bioactivity. You’re simply looking for compounds that are, frankly, poisonous in isolation, and enough of any poisonous compound will kill cells by itself. However, in a plant like hawthorn it appears that both flavonoids and procyanidins have beneficial bioactivities, and that multiple compounds in each class are bioactive, so you are not likely to be able to fish out one molecule and get the same complex in vivo activity profile.

    Also, in nature the presence of multiple antipathogenic compounds probably has the advantage of delaying the evolution of resistance. We only use an antibiotic or pesticide for a few decades before seeing major resistance, whereas plants seem to get by for millennia. (Likewise, Peruvians used quinine bark effectively for malaria for a long time, but once Europeans started using isolated quinine, resistance developed in less than a century.) We are now starting to push multidrug malaria treatments for that very reason. Maybe we should have been emulating the plants all along and using multiple compounds.

    I do have a question; you say “In the vast majority of cases, fractionation of plant extracts leads to an enrichment of cytotoxic activity.” That could mean either that the concentrated fraction is more toxic than the crude extract when given in equal volumes (which means that a far higher quantity of the toxic molecule(s) is present), or that the concentrated fraction is more toxic than the crude extract when given at a much lower dose, so that the dose of the toxic molecule(s) is identical. In the former case, it’s not a surprise that higher dose means more toxicity. In the latter case, it actually implies that other molecules in the crude extract interfere with the toxicity of the “active molecule,” which is supporting evidence for the idea that whole plants may be less toxic because they contain multiple compounds with opposing effects. (Real life example: ginseng contains individual ginsenosides that both raise and lower blood pressure in animal studies, but as a whole extract tends to lower blood pressure.)

  57. “I am simply fascinated by the promise of herbal mixtures and their components as a source of novel chemistries that have allowed us to find new mechanisms of action to treat diseases.”

    That’s really the point, isn’t it? The non-woo view of herbs as potential medicines.

  58. David Gorski says:

    Indeed it is.

    However, one thing about the “CAM” movement is that it tends not to e interested in the hard, involved science necessary to identify the active compound(s) in the herbs and how they may act and interact. Rather, its advocates have a distressing tendency to simply assume that because a remedy is an herb or part of a plant it must be better than pharmaceutical products, even herb- or plant-derived drugs, because it’s “natural.”

  59. apteryx says:

    I don’t assume that willow bark is better than aspirin, opium is better than codeine, or artemisia is better than artemisinin (if you can afford the drug and, where it is prescription-only, gain an MD’s permission to obtain it). However, I do assume that hawthorn is better than a NONEXISTENT drug derived therefrom. Some proven benefit is better than no benefit. I also think that if a manufacturer did make a single-compound drug from a complex botanical, it should be their job to demonstrate that it is better than the plant it came from, rather than asking us all just to “simply assume” that the brand new corporate product is superior.

    I, for one, am very interested in the “hard, involved science” that is used to demonstrate these plants’ bioactivities, whether or not the studies of bioactivity identify single active compounds. Lab studies supporting traditional uses are great to see, because animals and isolated cells can’t be accused of experiencing placebo effects! Animal studied and in vitro mechanism studies are hard and involved, indeed, but I hope you don’t mean to imply that if they can’t completely explicate all mechanisms of action, they will never be “hard” enough to satisfy.

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