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News flash! Doctors aren’t all compliant pharma drones!

There’s an oft-quoted saying that’s become a bit of a cliché among skeptics that goes something like this: There are two kinds of medicine: medicine that’s been proven scientifically to work, and medicine that hasn’t. This is then often followed up with a rhetorical question and its answer: What do call “alternative medicine” that’s been proven to work? Medicine. Of course, being the kind of guy that I am, I have to make it a bit more complicated than that while driving home in essence the same message. In my hands, the way this argument goes is that the whole concept of “alternative” medicine is a false dichotomy. There is no such thing. In reality, there are three kinds of medicine: Medicine that has been shown to efficacious and safe (i.e., shown to work); medicine that has not yet been shown to work (i.e., that is unproven); and medicine that has been shown not to work (i.e., that is disproven). So-called “complementary and alternative medicine” (CAM or, its newer, shinier name, “integrative medicine”) consists almost completely of the latter two categories.

Part of the reason why this saying and its variants have become so commonplace among those of us who support science-based medicine is that they strike at a common truth about medicine, both science-based and “alternative.” That common truth is what we here at SBM have been arguing since the very inception of this blog, namely that there must be one science-based standard of evidence for all treatments, be they “alternative” or the latest creation of big pharma. That point informs everything I write here and everything my blogging parters in crime write about too. What that means is a single, clear set of standards for evaluating medical evidence, in which clinical evidence is coupled to basic science and scientific plausibility. Indeed, one of our main complaints against CAM and its supporters has been how they invoke a double standard, in which they expect their therapies to be accepted as “working” on the basis of a much lower standard of evidence. Indeed, when they see high quality clinical trials demonstrating that, for example, acupuncture doesn’t work, they will frequently advocate the use of “pragmatic” trials, lower quality trials of “real world effectiveness” that do not adequately control for placebo effects. It’s putting the cart before the horse.

If there’s another aspect to the tactics of those hostile to science-based medicine, it’s that they really, really don’t like big pharma. Indeed, I can’t recall how many times, I’ve been called, in a typical knee-jerk fashion, a tool or minion of big pharma for pointing out that this CAM modality or other is without a basis in science, so much so that I even coined a term for it: the pharma shill gambit. None of this is to say that big pharma is not guilty of abuses of science. I’ve written about them. Steve Novella’s written about them. Our friend Ben Goldacre, who is well known as a critic of unscientific medicine, writes about them regularly and just released a book about them entitled Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients. Other SBM bloggers and skeptics have written about them. Still, CAM proponents try to make this label stick to their critics as an ad hominem attack that ignores whether our arguments have validity in favor of poisoning the well; it’s a particularly favored tactic of antivaccinationists.

Admittedly, however, Steve, Ben, our SBM bloggers, and I are not typical physicians. We are active in the skeptical movement and spend considerable time and effort writing and speaking about issues of skepticism, science-based medicine (SBM), and bad science. What about more typical physicians? How do they view these issues? CAM supporters like to paint a picture of doctors as mindless drones who do whatever their big pharma paymasters tell them to do, prescribe what they’re told to prescribe, and shun “alternative medicine” and CAM, just as they’re told to do. (If you don’t believe me, just peruse Mike Adams’ NaturalNews.com or Joe Mercola’s website for a while.) That’s why I was particularly amused by a study that’s hot off the presses in the New England Journal of Medicine by Kesselhem et al. entitled A Randomized Study of How Physicians Interpret Research Funding Disclosures.

After noting the trend towards increasing disclosure of funding sources and increasing rigor in (and therefore frequency and prominence) disclosing these sources in medical journals (a trend, I note, that I fully support), Kesselheim et al. note:

The methodologic rigor of a trial, not its funding disclosure, should be a primary determinant of its credibility. Skepticism about results that is based on a trial’s funding sources may be less appropriate for well-controlled, double-blind, randomized trials than for poorly controlled or unblinded trials, in which conflicts of interest may have a stronger effect on interpretation of the data. However, little is known about how information concerning study design interacts with information concerning funding sources to influence physicians’ interpretation of research. We therefore conducted a randomized study involving simulated research abstracts to assess the role that disclosure plays in physicians’ interpretation of the results of medical research.

Although I tend to agree that the design of a study should be the primary determinant of how that study is evaluated, one can’t help but note that selective reporting of results can taint even the best designed trial. So, although I agree that the funding source might be less of a problem in large, well-designed trials, I think that Kesselheim et al. might be a bit too quick to dismiss it. Fortunately, that isn’t the focus of their study. Their focus is to ask what the effect of funding source disclosure is on how physicians interpret the literature right now.

To do this, Kesselheim et al. decided to test their hypothesis that knowledge of the funding source of a study affects how physicians interpret that study. They thus developed hypothetical scenarios in which three new drugs were evaluated for the treatment of common disorders seen by primary care physicians: angina, diabetes, and hyperlipidemia. Three fake drugs were dreamed up, with a set of fake abstracts to go with them describing studies of various methodological rigor thusly:

“Lampytinib” would be used for dyslipidemia in patients who had unacceptable side effects from statins, “bondaglutaraz” would be used for diabetes and low levels of high-density lipoprotein cholesterol in patients who were taking metformin and a sulfonylurea and who were unwilling or unable to add insulin, and “provasinab” would be used for angina in patients with untreatable multivessel coronary disease who were taking maximal doses of beta-blockers. Since internists report that they frequently read only the abstracts when reviewing the medical literature, we created abstracts describing trials of these drugs in which we varied the drug being tested, the trial’s methodologic rigor, and the funding source. For each drug, one trial had a high level of rigor, one had a medium level of rigor, and one had a low level of rigor. The features defining these levels were based on guidelines and on our experience in conducting randomized trials and in studying evidence-based drug-evaluation and prescribing practices…

Differences in methodologic rigor among the trials were consistent across drugs. All the trials had similar effect sizes, and statistically significant results.

We then added a variable describing the trial’s funding status. Each abstract included one of three variations: no funding source mentioned, funding by the National Institutes of Health (NIH), or funding by a pharmaceutical company, with financial involvement in that company on the part of the lead author. (Companies named in the disclosure statements were randomly selected from the top 12 global pharmaceutical enterprises.)

This process resulted in 27 different abstracts with a variety of methodological rigor and different funding sources. The authors then recruited subjects from the American Board of Internal Medicine mailing list, starting with a potential sample of over 45,000 physicians and whittling it down to 503 who reported spending at least 40% of their time per month in patient care activities, less than 50% of which could be in the emergency department, intensive care unit, or cardiac catheterization lab. Physicians in the sample then received two postcards and three e-mail messages from the ABIM stating that they had been randomly selected to participate in a study investigating how physicians make prescribing decisions. The e-mails contained the names of the lead investigators and sponsoring institutions, a link to the online survey, an opportunity to opt out, and an offer of a $50 honorarium for completing the survey. These were followed up with a printed version of the invitation and a telephone reminder.

Those who agreed to participate were presented with three abstracts:

Participants were presented with three abstracts, each of which described a trial of a different hypothetical new drug. Participants were told to assume that the hypothetical drug had recently been approved by the Food and Drug Administration and was covered by insurance and that the abstract was from a “high-impact” biomedical journal and written by academic physicians at established U.S. universities. We randomly varied the level of methodologic rigor and the disclosure so that the three abstracts that the physicians received described trials at each level of methodologic rigor and with each disclosure variation.

The selection of abstracts can be found in the Supplemental Data, along with the survey questions.

The response rate (53%) was surprisingly good for an online survey. (Quite frankly, I almost always ignore these things when I get them. I realize that I shouldn’t, at least not always, but there always seems to be something I have to do.) Also, reassuringly, there was a strong correlation between the physician respondents’ perception of the methodological rigor of the trials and the actual methodological rigor of the trials. (If there were not, it would be…bad.) Physicians were more likely to prescribe drugs supported by high-rigor trials than medium-rigor trials and less likely to prescribe drugs supported by low-rigor trials than by medium-rigor trials. So far, so good. There’s nothing surprising here.

Next, the authors looked at how the funding source affected the physician’s perception of their willingness to prescribe new drugs. What do you think they found? Did the revelation that a trial was funded by pharma affect physicians’ willingness to prescribe a new drug? If so, how? If you believe Mike Adams, it either shouldn’t matter or physicians would eagerly compete to prescribe a new drug, just as their pharma masters tell them to. It’s a good thing that most readers here don’t believe Mike Adams (I would say all readers, except that there are a few trolls here who clearly subscribe to Mike Adams’ silliness), or they’d be surprised at the results.

It turns out that physicians view pharma funding sources negatively, and the revelation of a pharma funding source for a trial resulted in the physicians reporting that they were less likely to prescribe a new drug than if the funding source was not reported or was reported to be the NIH:

We found clear associations between the funding disclosure variations and physicians’ perceptions of a trial’s rigor and results. Regardless of the actual study design, physicians were less likely to view a trial as having a high level of rigor if funding by a pharmaceutical company was disclosed than if no disclosure statement was included (odds ratio, 0.63; 95% CI, 0.46 to 0.87; P=0.006) Similarly, in comparisons with trials for which no funding was listed and regardless of the study design, physicians were less likely to have confidence in the results of trials funded by industry (odds ratio, 0.71; 95% CI, 0.51 to 0.98; P=0.04) (Figure 2B) and were less willing to prescribe drugs described in such trials (odds ratio, 0.68; 95% CI, 0.49 to 0.94; P=0.02) (Figure 2C). These effects were even greater when industry-funded trials were compared with trials described as having NIH support.

Not only did doctors tend to downgrade the rigor of a trial if pharmaceutical funding were revealed, their confidence in the trial, and their willingness to prescribe the drug, they were half as willing to prescribe drugs studied in industry-sponsored trials as they were to prescribe drugs studied in NIH-funded trial by a ratio of two to one. True, this is a survey, with all the attendant difficulties and pitfalls of surveys, but it does “ring true” to me and to, I bet, many other physicians. Indeed, it almost reaches the level of a “Well, duh!” result. Most physicians do tend to be much more skeptical of pharma-funded trials than of other trials. I was, however, surprised by the strength of the effect in this particular survey. This is not by any means a weak effect. If it is in any way representative of the bulk of practicing internists out there, it actually represents a major problem for the pharmaceutical industry, as the authors of this study point out:

These findings have important implications. Despite the occasional scientific and ethical lapses in trials funded by pharmaceutical companies, it is also true that the pharmaceutical industry has supported many major drug trials that have been of particular clinical importance. Excessive skepticism concerning trials supported by industry could hinder the appropriate translation of the results into practice. For example, after publishing the results of a large, well-designed trial describing a new use for a widely prescribed class of drugs, a leading biomedical journal noted that many of its readers believed that the results of the trial did not justify a change in clinical management, citing industry funding as a key reason for this conclusion.

And I actually agree with this. Given the well-known lapses in ethics and deceptive research in the pharmaceutical industry, it is by no means a simple question to determine how much weight to assign to a funding source disclosure. If the magnitude of skepticism exhibited by the physicians in this survey — based solely on knowing that a study was funded by pharma — is anywhere near what typical physicians exhibit, it might be too much. My first thought reading this study was that perhaps the reluctance to change prescribing habits was nothing more than the well-known conservatism of physicians. Few of us change practice based on a single clinical trial. There are exceptions (for instance, the Z0011 trial about the need for axillary dissection after a positive sentinel lymph node biopsy in breast cancer resulted in a near-immediate change in practice in most academic medical centers), but in general it takes several studies before most physicians come to be convinced that a new treatment is better than the old treatments.

On the other hand, this study also made me wonder if perhaps we place too much confidence in research funded by the NIH. It is true that the NIH uses very rigorous peer review to decide what research is funded. It is also true that, these days, competition for NIH grants is more intense than it’s been in at least 20 years, if not more intense than it’s ever been, because of the paucity of funding, a situation that looks as though it will not get better any time soon and might well become very worse very soon if the “fiscal cliff” issue is not resolved. Be that as it may, while the current tight funding process in the NIH does tend to make sure that crappy studies are less likely to be funded, it also imposes a troublesome conservatism on science simply because there is not money to spare for “riskier” projects. Even so, NIH funding is not a guarantee of quality science by any means. Just peruse this blog for studies funded by the National Center of Complementary and Alternative Medicine (NCCAM) for ample evidence of this. (As an aside, CAM advocates know that doctors trust the NIH and NIH-funded studies more than other studies; that’s the whole reason they supported the creation of NCCAM in the first place. But I digress.)

There is no doubt that there is considerable evidence that pharma funding is associated with an increased likelihood of publishing results favorable to the company funding the trial and contributing to publication bias, although this evidence is sometimes conflicting. For example, a recent study found a correlation with government funding of a trial and positive results, and another study found no higher likelihood of positive outcomes in industry-sponsored trials but a higher likelihood of reporting double-blinding, an adequate description of participant flow, and performance of an intent-to-treat analysis. (This latter study did, however, find a trend towards higher probability of nonpublication of industry-sponsored trials, suggesting contribution to publication bias.) Moreover, several studies have suggested that from a methodological standpoint industry-funded studies published in peer-reviewed journals are of equivalent or higher quality than clinical trials funded by other mechanisms. This is not surprising, given that many clinical trials funded by pharmaceutical companies are done for the purpose of winning FDA approval for a drug, either initially or for expanded indications, and the FDA has stringent requirements for these clinical trials.

So what to do? There’s no doubt that, to a large extent, pharmaceutical companies have brought this level of distrust on themselves. Indeed, as I mentioned, this NEJM study doesn’t tell me anything that I didn’t already know: namely, that most doctors read industry-sponsored studies much more skeptically than they do NIH-sponsored studies and are much less likely to have confidence in them and use them to justify a change in medical practice. It is nonetheless useful in that it provides some measure of hard evidence to support this observation. More importantly, it tells us that it probably isn’t a small effect. (Indeed, it would have to be large to be noticed just in daily practice and discussions of studies that doctors routinely engage in.) I also know that most doctors understand that much of what is published in the medical literature ends up being wrong; so that contributes to the caution we all exercise in evaluating new medical literature.

All of this brings us back to the question of what is the appropriate amount of additional skepticism towards new studies that we should exercise when those studies are pharma-funded above and beyond the skepticism we normally exercise for studies funded by other sources? Thinking about it a bit more, I’ve come to the conclusion that most doctors, at least in this sample, probably have it about right or may even be a little more skeptical of pharma than necessary. I’m also satisfied to know that, contrary to Mike Adams’ caricaturing, my colleagues are not all mindless pharma drones — not by any stretch of the imagination.

It leaves more filthy pharma lucre for me.*

*In case it wasn’t painfully obvious, that was a joke, people. I’m not Mark Crislip. So sue me. Besides, my price would have been too high. I would have wanted a guarantee of a new iPhone 5 delivered to me at 9 AM on launch day. As it is, I have to wait until Wednesday or Thursday for mine to be delivered. I mean, what’s a pharma conspiracy if it can’t get its minions the latest tech toys right on launch date? Am I right?

Posted in: Clinical Trials, Pharmaceuticals, Politics and Regulation

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205 thoughts on “News flash! Doctors aren’t all compliant pharma drones!

  1. Janet Camp says:

    As I sit here downloading my iOS 6 operating system (into my now hopelessly dated iPhone 4S) and wondering if I will regret the map app coming with it), I am feeling very tired from staying up very late to try to write an effective response to the enormous load of stinking dingo kidneys that followed an open letter from the Mayor of Portland (Oregon) who issued said letter prior to his vote to add fluoride to Portland drinking water.

    I was alerted to this letter by our good friend Dr. Barrett of Quackwatch. The letter included intelligent, respectful, and documented responses to at least a dozen (mostly completely whacky) objections to fluoride, many of which probably originate from places like NaturalNews.

    The comments that followed were overwhelmingly full of bad (really bad) grammar and even worse levels of critical (or any) thinking. The overuse of exclamation points, truly filthy language, and outright threats were at high levels. Long spam type of posts were double and triple posted, some using the title doctor without saying of what. One ends up hoping that the addition of fluoride will do something about the insanity that grips some portion of the population of my former home city. I remember having to get the fluoride pills and pay for lots of supplemental treatment at the pedodontist for four kids due to this lack of modern public health policy in Portland.

    The overriding complaint was the “health freedom” gambit, but “pharma shill” was right up there as well. Dentists, of course, (“mainstream” ones, anyway) are an evil cabal (is that redundant?) of pharma and government overlord shills. You will be happy to find out that fluoride is a DRUG and about to become a forced medication that will be poisoning the water supply against the will of the people, who were cruelly and surreptitiously denied the right to vote directly about the matter! They are getting ready for a referendum and they only need 20,000 signatures–but only have 30 days to get them.

    A few brave souls complimented the Mayor on his research and ultimate decision favoring science, but they were exposed quickly as mindless nazis obviously in the thrall of….well, you know the drill. I’m just so glad that my grandkids are across the Columbia in long-time fluoridated Vancouver, Washington.

    So I’m glad to hear that doctors seem to be up to speed, but we have a ways to go with the public. I would like to know what percent of the Portland population this response represents? Dr Crislip, can you offer any insights?

  2. nybgrus says:

    I’ve read Goldacre’s article in The Guardian (actually before I came across this here on SBM) and have added the book to my Amazon wishlist.

    I personally find the issue to be daunting. We know pharma companies engage in unethical practices, don’t publish or make available negative data, hide side effects, and play games with regulations and laws (including ghost writing and studies in devolping nations). But, as Ben says, we don’t know how much and how often they actually do this. We do know that drugs work – and often work incredibly well. That statins are effective in reducing CV mortality is nearly a definite at this point. They have been around long enough, have enough non-industry studies, and massive meta-analyses. But for other drugs, especially new ones, how much don’t we know about the potential side effects and the true effect sizes?

    I reckon that the level of skepticism – in terms of changes practices and giving drugs – is probably appropriate. I certainly don’t think that you can argue it is too much – we are forced to being overly conservative because we simply don’t know what we don’t know. In a hypothetical scenario where we are omniscient and know exactly what is being with held and manipulated then it can be asserted that we are too skeptical or not enough. But in the face of simply not knowing if these transgressions are merely the tip of the iceberg or most of it (nor even how big the iceberg is) I think it is hard to say we are being too skeptical.

    For argument’s sake I’d ask what about being even more skeptical to make the pharma companies earn back our trust as a necessary step to protect their bottom line? If we don’t prescribe, despite them spending gajillions of dollars on studies because we can’t trust them, then we shift their bottom line and the means to get there. I know it is vastly more complicated than that, but it seems like a start – something our professional associations could get on.

    From my (novice) perspective, I would view pharma funding as providing me two things. A reason to read the study much more carefully and (with the possible rare exception) never making the drug my first or even second line choice. I may conclude that the study was still reasonably done (though Goldacre demonstrates how apparent effects can be completely manufactured) and that the drug may be effective for a condition. But I cannot trust that I know the full picture of the risk nor the true magnitude of the benefit. To make something first or second line I would need to be able to make an assessment on that. Once you get to 3rd line drugs you are already in a situation where risks become much more likely to be outweighed and thus it becomes an easier choice to make.

    No matter how one slices it, however, this is an area where reform is certainly needed and scientific integrity and intellectual honesty need to rule the day. Unfortunately the harms these days are not as clear cut as the were back in 1905 leading to the creation of the FDA in the first place* so I am less hopeful that a massive uprising of the people will clamor for this change. That leaves it to us to push the issue as best we can.

    *I recently toured a pharmacy museum in my current town of residence. It is the oldest pharmacy in the US featuring the first ever licensed pharmacist. It was impressive to see how far we have come. My better half was stunned out how things used to be and was in thrall remembering the various things I tell her about in my own studies. An interesting example was a pacifier (or binky, if you prefer) for babies with a cleft lip… made out of lead. It was noted at the time that lead seemed to quiet the babies down better. As did the heroin/opium colic tinctures that were used. We forget just how far we have come in such an incredibly short time and, to use an expression from my current locale, have probably grown a bit too big for our britches. I suppose though, that when people think statements made by Presidential hopefuls “all the way back in May” is ancient history not pertinent to the discussion 100 years seems like geologic time. Maslow’s needs have been met in spades and the decadence of a 140 character world has spoilt the conversation. I think, however, that overall we are still progressing in the right direction… we just need as many as possible to keep up the solid work.

  3. Mark Crislip says:

    I just figure every study in the real world is half as good as reported; the big pharma/bias discount I apply to every literature purchase. Makes the results of SCAM studies particularly unimpressive

  4. WilliamLawrenceUtridge says:

    I persist in believing that a better system would involve the money spent by Big Pharma to conduct trials of new drugs being given to a third party (almost certainly government) who would run the trial instead, publishing all data freely. If you could convince the FDA and other regulators that drugs could only be licensed by trials passing through such a system, all the better. You would have to create another layer and system of bureaucracy, but the value of a third-party running actual trials and publications would probably more than offset this.

  5. windriven says:

    @Janet Camp

    “I’m just so glad that my grandkids are across the Columbia in long-time fluoridated Vancouver, Washington.”

    Perhaps you have stumbled onto a previously unknown benefit of fluoridated drinking water: improved mental health. As you certainly know the unofficial motto of Portland is, “Keep Portland Weird” while the unofficial motto of fluoridated Vancouver, WA across the river is, “Keep Vancouver Normal.”

    Kind of makes one wonder… ;-)

  6. David Gorski says:

    I just figure every study in the real world is half as good as reported; the big pharma/bias discount I apply to every literature purchase.

    Except for my studies. My studies are always more awesome than what appears on the pages of the peer-reviewed journal. :-)

  7. Janet Camp says:

    @windriven

    Ha! That’s pretty much what my comment said at the end of all the craziness posted in response to Mayor Sam Adams’ letter. I’m so old now that I only remember Portland being called “The Rose City”, and Vancouver was, well, just Vancouver–where you had to pay sales tax.

    Where did all these people come from? Obviously, there’s always the inflow from California, but a surprising number of the “weird” come from…drum roll…Michigan, Minnesota, and Wisconsin. So there you have it–proof, proof I tell you, that fluoride causes insanity once you withdraw it from the water supply–or withdraw the users from the treated water. So stay “normal” in Vancouver. ;-)

    Just an afterthought thought–if the fluoride is at .07 per million, is that homeopathy (or as good as version as some of what is marketed as such)? Kinda goes with your observation WD. So wouldn’t whatever evil effects are being subscribed to fluoride have the opposite effect on the population? The Mayor also promised (and gave evidence) that the fluoride won’t affect the beer–and if you believe that..well, you really are an evil pharma shill. :-)

    I totally apologize for digressing.

  8. Purenoiz says:

    I have a question I feel is legitimate regarding the pharma shil gambit. I’ll start by prefacing the fact that Dr Gorski wrote another entirely awesome screed on this study. However I heard something, so yes it is a rumor, so humor me., and please only the doctors chime in on this one as they are the ones to know. Do doctors ever receive kick backs or compensation for prescribing medications from the pharmaceutical companies?

    This is not to be confused with the practice of paying Dr’s for lecturing about a pharmaceutical, nor is it a to be confused with gifts etc. Can GP’s actually make money off of prescribing a particular agent, be it beta blockers, statins etc.?

    1. Harriet Hall says:

      @Purenoiz,
      No one ever offered me a way to get kickbacks for prescribing a drug, and I’ve never heard of anyone I know being offered any kind of kickbacks. I’ve read about accusations, but if it happens, it’s clearly illegal and is prosecuted.

  9. NathanAlexanderRice says:

    Some issues, from the perspective of a scientist:

    Most alternative medicines are “evidence based” to some degree, unfortunately knowledge of the placebo effect is fairly recent, the statistics required for good trials can be a little bit complex, and isolating/controlling variables is often a challenge. We do a better job of this than we used to, but I see so many horribly designed studies that I hesitate to say we’re good at it yet. “Alternative” medicines that have survived for hundreds (or even thousands) of years do so because people see value in learning them; I hesitate to dismiss hundreds of years of trial and error until a significant body of well designed and executed research weighs in to the contrary. There are a few cases like crystals, “energy” massage and homeopathy that really have no conceivable mechanism of efficacy where I agree with you completely.

    The publication bias is amplified by the amount of money available to research something. The pot for CAM is a lot smaller. If you accept a p value of 0.05, and pharma funds 20 studies for every CAM funded study, of course they are going to come out looking pretty good. I’m not saying this is the only factor, but it should be kept in the back of your head.

    At the end of the day, the only thing that should matter is “is your patient getting better”? If a particular treatment is very effective at eliciting a strong placebo response for whatever reason, does that make it less valuable than a non-placebo treatment with more side effects? Are we actually advancing the state of medicine if we destroy people’s perception of the placebo treatment? What about when we say that we have no reason to believe a medicine works, just because no clinical trials have been performed with it, despite hundreds of years of continued use? Perhaps we should instead say we have no scientific evidence showing its efficacy is due to the placebo effect.

  10. laproxdoc says:

    @Purenoiz,

    Way way back in about 1974 in the summer after completing general surgical residency and fellowship but before going on active duty in the US Navy I worked as a GP/GS in a small town in rural western Washington covering a physician taking a well deserved 2 month vacation. One particular pharmaceutical rep was all over me: there was no talk of kickbacks, but everytime he learned from the hospital’s pharmacy that I had prescribed one of his company’s products he would come by bearing gifts: he would invite me to dinner at better restaurants, offer me tickets to professional sports events in Seattle, and even offered to broker a discount at a nearby luxury car dealership amongst other things. He had a great gift of gab and it was very enlivening to talk to him. I never accepted. If I had stayed there longer especially into the dark rainy Pacific northwest winter I might perhaps have gotten soft around the principles and justified accepting some of these “gifts” as a diversion. I was never in a rural setting again so I do not know if that sort of thing continued, however no one ever blatantly offered me any benefits besides ballpoint pens during 33 years in group practice in San Diego. Sigh.

  11. WilliamLawrenceUtridge says:

    Hi Nathan,

    Are you a newcomer to this blog? If so, I suggest reading some of the back-links as there are numerous objections to some of your points. For instance, “is your patient getting better” is essentially what sustained nonscientific medicine for years. It’s patronizing and unethical, harkening back to the days of paternalistic medicine. The use of unproven “medicine” is, if harmless, still a waste of time and money and often serves to introduce patients to the CAM mentality which is itself based on a negative assertion – opposition to real medicine rather than evidence-based demonstrations of efficacy. CAM can lead to rejecting conventional treatment, often its most dangerous effect, and that can kill. For instance, see this post on SBM.

    You could also try searching for the word “shruggie”, which seems to be your position. Though far better a position than actively promoting CAM, it still presents risks to patients.

  12. David Gorski says:

    “Alternative” medicines that have survived for hundreds (or even thousands) of years do so because people see value in learning them; I hesitate to dismiss hundreds of years of trial and error until a significant body of well designed and executed research weighs in to the contrary.

    Ah, the argument from antiquity. This one is fairly easy to deal with using a counterexample or two (or three). Let’s see. What should I start with first? Oh, I know: Bloodletting. Bleeding for virtually everything that ailed anybody “survived for hundreds (or even thousands) of years do so because people see value in learning” it. Indeed, bloodletting only fell into disfavor maybe 150 years ago at the most, maybe even more recently. Now, how about another example? I know the perfect one: Homeopathy! Most homeopathy is nothing more than water or the diluent used to dilute a homeopathic remedy into nonexistence, and it’s persisted for well over 200 years now. How about another example? Hmmm. Faith healing. Yes, faith healing has been around for hundreds, if not thousands, of years. Indeed, one alt-med that’s currently popular, namely reiki, is nothing more than faith healing. (Don’t believe me? Substitute “God” and the “power of God” for the “universal source” and the “healing energy” that comes from that “universal source” in reiki, and the resemblance is unmistakable. Reiki is faith healing that substitutes Eastern mysticism for Christian beliefs as its basis.)

    So, here’s the deal. Just because a treatment or type of medicine has existed hundreds or thousands of years does not mean it must have some value. There are lots of examples of medicines that have been around that long that clearly do nothing or even cause harm. In other words, the argument from antiquity is a bad argument.

  13. Robb says:

    I think one of the points Nathan was trying to make is that lack of evidence does not equal lack of efficacy, especially given the global difference in research funding available. Of course, historical use of something alone is not enough to justify using it at the expense of a current research proven treatment, especially the more serious the health condition is. Historical use/empirical evidence of something is just part of what makes up the whole context of human use – or, put another way, the bottom of the evidence based pyramid for “what works”. In cases of say, treating cancer, it would be crazy to rely on historical use alone, but in other examples, say you’re experiencing indigestion with gas, bloating, cramping – you’ve read that peppermint and fennel have long been used for that, there’s some small studies reinforcing the historical use, there’s a plausible mechanism of action, it’s not a life threatening condition, etc. In a case like that, why would I wait for an RCT to tell me whether I should try it or not?

    I think part of the problem is that too many completely disparate things get lumped into a CAM umbrella when they have no relation to each other and that too many CAM “things” attempt to treat or claim to do things they are not able to. Personally, my background is in herbal medicine and related research and I know the importance of not overstating what it can and can’t do. I do like the position of many here that there is no such thing as CAM, just medicine that works and medicine that doesn’t (or hasn’t been proven to yet). A lot of that position hinges on what you define as “medicine” though. I wouldn’t call food medicine, although it’s obviously crucial to good health. If you define medicine as simpy agents that treat pathologies effectively, then, while it is succinct and convenient, reality isn’t as black and white as that and you have sub-clinical pathologies – you don’t go from 100% healthy to full blown disease state – it’s on a spectrum. A lot of herbs and supplements do their best in that middle ground between food and drug, between full health and full pathology – thus the structure/function claims that they make within the regulatory framework in North America, Europe, and Australia/NZ.

  14. Purenoiz says:

    Harriet and Laproxdoc,

    Thanks for the heads up. I will try to get some clarity from my girlfriend, she interviews doctors to see if they are a good fit personality wise, and that they have her best interest at heart.

    Just out of curiosity Harriet, what would they be prosecuted for?

  15. WilliamLawrenceUtridge says:

    Dr. Gorski, don’t forget simple magic. Ancient Egypt, which had a relatively highly developed medical system that modern research indicates might actually help in certain circumstances, was based equally on specific interventions (raw meat on wounds to speed clotting, trepenation) and prayer. In fact, prayer probably has the longest documented history of any medical intervention. I forget, is there evidence it works?*

    In other words, the argument from antiquity is a bad argument.

    It’s not even an argument – it’s a fallacy.

    Robb, the whole point of this blog is that prior probability should underscore things like where we should put our scarce research resources. Realistically, we can pretty much dismiss anything from before the germ theory of disease and microscopes. Herbal medicine is pretty much the one CAM modality that is seen as having any merit, but as has been said here many times it is redundant to pharmacognosy. It still isn’t even medicine, since it’s still mostly old wives tales and unproven assertions. Until a specific herbal preparation has undergone scrutiny via pharmacognosy, you still don’t know whether you’re doing any good or just wasting time and money. And bundled with that waste must be recognition of the company kept by herbal medicine – if you believe in it, you’re more likely to endorse or recommend things substantially or actually worthless things like homeopathy, acupuncture, reiki, laetrile, Hulda Clark’s “zapper” and other such nonsense. As said by Dara O’Brien, we tested it and what worked became medicine. Everything else is a bowl of soup and some potpourri.

    *I kid, I know it doesn’t.

  16. Harriet Hall says:

    @purenoiz,
    “what would they be prosecuted for”

    I think it is the drug companies that are prosecuted. Doctors could be disciplined by their medical boards for unethical behavior, but that’s not likely to happen.

  17. Scott says:

    in other examples, say you’re experiencing indigestion with gas, bloating, cramping – you’ve read that peppermint and fennel have long been used for that, there’s some small studies reinforcing the historical use, there’s a plausible mechanism of action, it’s not a life threatening condition, etc. In a case like that, why would I wait for an RCT to tell me whether I should try it or not?

    This rather misses the point. Few people would argue that it’s unreasonable for you to try it. What we do argue, however, is that it is grossly inappropriate (some would say outright fraud) for someone to SELL peppermint and fennel as cures for such symptoms without actual evidence.

  18. Robb says:

    William: “It still isn’t even medicine, since it’s still mostly old wives tales and unproven assertions. Until a specific herbal preparation has undergone scrutiny via pharmacognosy, you still don’t know whether you’re doing any good or just wasting time and money. And bundled with that waste must be recognition of the company kept by herbal medicine – if you believe in it, you’re more likely to endorse or recommend things substantially or actually worthless things like homeopathy, acupuncture, reiki, laetrile, Hulda Clark’s “zapper” and other such nonsense.”

    If you think herbal medicine is mostly based on old wives tales, you have never really looked into the subject.
    I also totally disagree with your “guilt by association” generalization. How did you come to that conclusion? Who is this “herbal medicine” entity you speak of that always acts and thinks in the way you attribute? I’m convinced of its value but I think homeopathy is hokum. I know it makes life (and arguments) easier to paint with broad strokes and stereotype but reality isn’t like that.

    Scott: Fraud? The point is, there is evidence in many cases. The level of evidence required before you accept it can be debated but in my specific example, the current level of evidence is already widely accepted as sufficient in order for it to be sold.

  19. Scott says:

    The current level of evidence is “accepted as sufficient” because Big Herb bought themselves some senators to get the DSHEA passed. In no rational or reasonable sense is it anything other than fraud in the overwhelming majority of cases. Even in the cases where there is some evidence of efficacy, it’s just crazy to prefer an impure preparation of unknown concentration (an herb) to a standardized purified known dosage (a pill).

  20. Harriet Hall says:

    @Robb,
    “If you think herbal medicine is mostly based on old wives tales, you have never really looked into the subject.”

    You misinterpreted what he said. Old wives tales are little more than anecdotes and they don’t become data until they are tested. Some old wives tales pan out, others don’t. He said herbal medicine is the one CAM modality that has merit, but that it is redundant to scientific phamacognosy.

    And the “guilt by association” is obvious: CAM lumps all its modalities together under one umbrella.

  21. anony mouse says:

    @Scott:
    That goes for supplements, as well. My wife prefers to take an “organic, whole foods” prenatal vitamin as opposed to the standard one. Not only does it cost 3x as much for the same number of pills, but you have to take 3x as many pills to get the same amounts of the vitamins and minerals. Somehow, all that impurity is “better” because its “more natural”. In what universe does that make sense?

  22. WilliamLawrenceUtridge says:

    And the “guilt by association” is obvious: CAM lumps all its paradigmatically incompatible modalities together under one umbrella.

    Added a minor edit there. The fact that a naturopath will inject homeopathic preparations into acupuncture points is an astonishing exercise in double-think or lack of thought.

    Robb, you may be different, you may be very conscientious (if I recall your comments correctly, you have stated your own concerns about TCM preparations, the species, preparation and packaging of specific compounds and the like), but the very nature of your profession is substantially unproven. The very fact that you feel the need to separate yourself from others in your profession, that you feel the need to take extra steps to ensure your products meet the safety and efficacy needs of your clients that are above and beyond what most others require – this is evidence and a tacit admission that your profession is based on dubious claims and often worse science. Good for you for taking these extra steps and incurring what is doubtless extra expense and bother that most clients probably don’t notice or appreciate. But a pharmacist doesn’t need to take them because 99.9% of the time he knows what he’s getting, what it’ll do, and what kind of quality control is involved.

    None of this applies if I’m mis-remembering your comments. I hope I’m not, because it indicates you are both thoughtful and conscientious – but science and medicine rest on premises tested against evidence, not anecdote and old stories. Herbal medicine is at best suggestive, believing historical use is proof is simply wrong.

    Also, everyone should click on Dara O’Briain’s youtube video. It’s tops.

  23. Robb says:

    Scott,
    So what you are saying is that you have reviewed the entirety of the evidence for herbal medicine and it is in all cases so lacking that the only way it can be legally sold is by a couple senators being bought out? Really?
    I’m not in the US myself but that sounds like the same kind of conspiracy theory regarding the revolving door between the FDA and pharmaceutical execs. I don’t know…maybe both cases have some degree of truth as far as influence.

    In any case, I don’t believe, and other regulatory agencies around the world (not just in the US) don’t believe, that herbs require the same standards, or should be treated the same as, pharmaceuticals. Part of the history of use thing is that they have been in our diet for that long, which goes a long way towards establishing safety, rather than some novel unknown compound. Secondly, they are not intended as primary treatments for serious diseases so, given their safety, a lesser level of current evidence is considered acceptable. Do I require an RCT on broccoli before I’ll eat it and consider it nutritious? Do I expect food manufacturers to do bioavailability studies to prove the nutrients listed in their nutrition facts panel are actually well-absorbed? No. Do I want some new compound that is supposed to save my life from cancer and comes with significant side effects to have a high level of research based efficacy? Of course. Do I expect that same level of rigor for something I take when I’m constipated, have some arthritis pains, insomnia, or indigestion? No. Why? Because I’m dealing with a known substance that is safe for something that is much less of a critical health issue, I am willing to accept a lesser level of evidence – not no evidence – but a lesser level.

    As far as an “impure preparation of unknown concentration” goes, maybe you are not familiar with the subject. GMP and government regulations require purity and known concentrations. If someone purchases an herbal product that is adulterated, uses a wrongly identified herb or the label doesn’t reflect amounts actually in it, then that is illegal and the means are there for them to be removed from the market. In the vast majority of cases, the purity and concentration are not an issue. Even making a cup of tea, you know the concentration of loose herb to water as a basic starting point. Standardization is a different subject and herbs differ greatly to drugs. Herbs work by way of multiple constituents working together (synergy) and isolating a single constituent to standardize doesn’t always produce best results. There have been some interesting studies done already to try to tease out exactly what is going on synergistically. Anyway, I suspect I’ve probably overstayed my welcome in dragging this off-topic so I’ll leave it at that.

  24. Robb says:

    William,
    While I appreciate your sympathetic tone, I suggest you stop making assumptions. You are shooting blanks. I do not see clients. I am not pretending to be a substitute doctor. I am involved in research on herbs though and am very familiar with the body of knowledge and with government regulations regarding their sale and use. Also, as I’ve said already, believing purely in historical use is not what I’m advocating. To repeat, empirical evidence is part of the pyramid of evidence, but it is the lowest level. It suggests there may be something to it, but it “needs more research”.

  25. Scott says:

    So what you are saying is that you have reviewed the entirety of the evidence for herbal medicine and it is in all cases so lacking that the only way it can be legally sold is by a couple senators being bought out?

    More precisely, the entire concept that herbs can somehow simultaneously BE medicines, but not subject to any standards of evidence for safety and efficacy, is so mind-bogglingly ludicrous that it can only happen via the purchase of favorable legislation.

    In any case, I don’t believe, and other regulatory agencies around the world (not just in the US) don’t believe, that herbs require the same standards, or should be treated the same as, pharmaceuticals.

    If pharmaceutical claims are being made for them, then they most certainly should.

    Do I require an RCT on broccoli before I’ll eat it and consider it nutritious?

    If you are going to claim that broccoli cures cancer, then absolutely you need robust RCTs before you can sell broccoli with that claim attached.

    Do I expect that same level of rigor for something I take when I’m constipated, have some arthritis pains, insomnia, or indigestion? No. Why? Because I’m dealing with a known substance that is safe for something that is much less of a critical health issue, I am willing to accept a lesser level of evidence – not no evidence – but a lesser level.

    Again, we’re not talking about TAKING it, but SELLING it by making claims that are unproven.

    As far as an “impure preparation of unknown concentration” goes, maybe you are not familiar with the subject. GMP and government regulations require purity and known concentrations.

    Even if it’s 100% pure plant, it’s impure and of unknown concentration. In many cases no active ingredient is even hypothesized, much less known, so there is no way whatsoever to have any meaningful standard.

    Herbs work by way of multiple constituents working together (synergy) and isolating a single constituent to standardize doesn’t always produce best results.

    [citation needed] Actual synergy is VERY rare, and even in the cases where it exists, it’s incredibly unlikely that a plant just happens to have the optimal ratios of various ingredients. Yet another reason herbal medicine really has no place in the world other than as a source of investigational leads for pharmaceuticals.

  26. Robb says:

    Scott,
    What do you mean “even if it’s 100% pure plant, it’s impure”? How does this even make sense?
    With most herbs that have had even preliminary research done on them, the ingredients are well known and most have a number that are considered most “active” and used as a basis for standardization. The German E Commision monographs or Dr. James Duke’s phytochemical database at the USDA agricultural research website are two examples off the top of my head that deal with detailing active ingredients. Any good reference book like Principles and Practice of Phytotherapy by (Simon Mills & Kerry Bone; pub. Churchill-Livingstone in 2000) does the same.

    Ah synergy vs. reductionism…far too big a topic to cover in a reply to a blog post on a completely different topic. In many scientific fields, reductionist “silver bullet” thinking is giving way to more complex, systems based approaches and I don’t think pharmacology is any different. I still chuckle when I read some of the simple minded cautions in pharmacy texts or databases regarding herb-drug interactions. For example, that red clover should not be taken with blood thinning medications because it is a source of coumarins. Never mind that di-coumarol was originally discovered due to sweet clover being spoiled with mold and that coumarins do not act like di-coumarol in any way. But I digress…your point was, I think, that “synergy is rare and/or unlikely to occur, therefore, herbs should just be raw materials for new drugs”?

    Synergy is quite common, not rare. Here are some citations concerning plant synergy if anyone at this point is still remotely interested:

    E. M. Williamson. Synergy and other interactions in phytomedicines. Phytomedicine, Vol. 8(5), pp. 401–409.2001
    Spinella M. The importance of pharmacological synergy in psychoactive herbal medicines. Altern Med Rev. 2002 Apr;7(2):130-7. Review.
    Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals.
    Phytomedicine. 2009 Mar;16(2-3):97-110. Review.
    Ohno T, Kita M, Yamaoka Y, et al. Antimicrobial activity of essential oils against Helicobacter pylori. Helicobacter. 2003;8(3):207-215.

    Generally, standardization and isolation of compounds leads to increased toxicity and side effects – also increased efficacy in some cases of course too. Synergy demonstrates that more can be made of with less though. Less of the actives are needed because their effects are boosted by secondary constituents. I probably don’t need to explain that. Pharmaceutical approaches are recognizing the importance of synergy as well and that the reductionist, single molecule approach isn’t always best when it comes to dealing with malaria and bacterial infections and cancer for example. I really do apologize for taking this off on such a tangent, but it came up and it’s a fascinating topic to me.

  27. Harriet Hall says:

    No matter how rare or common synergy is, it can’t be assumed, but must be tested for in each individual case.

  28. BillyJoe says:

    Scott,

    “Few people would argue that it’s unreasonable for you to try it. ”

    Why would you “try it”?
    If there is no evidence that it works, why would you “try it”?
    Why would you not use something that does have evidence that it works?

    Someone once asked me “but have you tried it”, and my response was, “you can’t see if something works by trying it, you have to do a clinical trial”

  29. nybgrus says:

    I am extremely tired after my second 14 hour day in the PICU so I simply don’t have the energy to respond in full, but suffiice it to say Robb is quite off the mark. As one small example:

    Generally, standardization and isolation of compounds leads to increased toxicity and side effects –

    Complete bollocks. Perhaps you would like to cite definitive and specific examples of drugs that become more toxic and have increased side effect profiles by purifying them. Perhaps you’d like to discuss vancomycin which still has a bad rap for being nephrotoxic because of impurities in the manufacturing process in the 60′s which no longer exist because the drug is now more pure. But, since this is a general effect you should have no trouble delineating the myriad drugs which follow the opposite pattern.

    Next up we have:

    What do you mean “even if it’s 100% pure plant, it’s impure”? How does this even make sense?

    Because, Robb, a plant has (to use the technical term) a bajillion compounds in it. Of varying amounts based on soil composition, environment, season, and specific species and subspecies. The vast majority of which are uncharacterized in their action and often difficult if not impossible to detect. So 100% echinacea or gingko or fennel or fenugreek or whatever is still an utter grab back of…. impurities.

    But, as we can see, you are clearly an herbal expert well versed in the science of the matter.

    Lastly:

    If you think herbal medicine is mostly based on old wives tales, you have never really looked into the subject.

    Once again, clearly an expert deduction. Because when gingko is recommended for use in memory improvement that is based on scientific data, not wives tales. Same with saw palmetto for BPH, black cohosh for menopause, echinacea for colds, and feverfew for headaches. Oh wait. Those were all used for those indications prior to actual scientific studies demonstrating that they don’t work for those indications.

    The fact of the matter is that the vast majority of herbal use is purely old wives’ tales – unless you would like to demonstrate a corpus of scientific data on herbs that pre-dates their usage for such indications (i.e. nobody heard of feverfew and studied it and discovered it worked well for headaches and then was advertised as such). Oh yeah, that does exist – it is called pharmacognosy and is part of the high throughput screening used to discover and create…. purified pharmaceutical agents!.

    I am exhausted so I bid adieu but I couldn’t resist going after such bad argumentation and clear lack of understanding… and I barely scratched the surface with those mere 3 examples.

  30. David Gorski says:

    Added a minor edit there. The fact that a naturopath will inject homeopathic preparations into acupuncture points is an astonishing exercise in double-think or lack of thought.

    It’s actually a modality that isn’t that uncommon in woo land. It’s called homeopuncture. I kid you not:

    http://scienceblogs.com/insolence/2010/02/26/your-friday-dose-of-woo-how-do-you-make/

  31. weing says:

    @nybgrus,

    I know a lot of herbs that have actual uses and effects. Cannabis, peyote, opium, coca leaves, hemlock, just to name a few.

  32. nybgrus says:

    @weing: fair enough. But what were they used for vs what does the science tell us to use them for now? I never said none of the current uses stemmed from old wives tales. But it is by far a minority. And did they become more or less toxic as we refined them from raw form to pharmaceutical grade?

    (I know you are playing devil’s advocate)

  33. weing says:

    @nybgrus,

    Isn’t it curious that none of them are found on the shelves?

  34. Scott says:

    What do you mean “even if it’s 100% pure plant, it’s impure”? How does this even make sense?

    It includes the actual active chemical(s), AND a bunch more.

    But I digress…your point was, I think, that “synergy is rare and/or unlikely to occur, therefore, herbs should just be raw materials for new drugs”?

    No. Synergy is rare. AND herbs should be just raw materials for new drugs.

    If anything, synergy makes standalone herbs LESS credible since it makes it even more vanishingly unlikely that whatever random conglomeration of stuff evolution happened to throw together for non-medicinal purposes can’t be improved upon by science. The idea that it’s even possible for herbs to have some kind of synergistic effect which cannot be replicated by isolating the active ingredients is straight-up false. 1+1=banana level false.

    Synergy is quite common, not rare.

    Williamson: Unfortunately I can’t access the full text; this is your only citation that looks vaguely credible based on the abstract. I do really wonder whether it deals with ACTUAL synergy or just “multiple active ingredients can stack.” True synergy means that there’s actual interaction where one ingredient improves the other’s effect. Multiple ingredients producing the same effect is just a bigger effective does, not synergy.

    Spinella: Completely speculative that synergy MIGHT be relevant in some cases and should be looked for. Not evidence that it is “quite common.”

    Wagner: Suggests that because herbal combinations are known to be more effective (gross begging the question), it must be synergy.

    Ohno: Abstract doesn’t even mention synergy.

    Still, synergy is a complete side question – since even in the cases where it exists, it provides zero rationale to use herbs.

    Generally, standardization and isolation of compounds leads to increased toxicity and side effects – also increased efficacy in some cases of course too.

    Gonna need REALLY good evidence for that, since this claim can be paraphrased as “adding a bunch of completely random other chemicals reduces toxicity and side effects.”

    Overall, I get the impression that you subscribe to the “God created herbs to be ideal medicines” philosophy as opposed to the reality that they contain whatever mix of chemicals evolution happened to produce – without selective pressure towards being effective medicine, so without any reason to believe any medicinal properties are more than coincidental. Is that so?

  35. Scott says:

    Apologies for the double post, but I wanted to add a brief summation.

    In the absence of specific testing for safety/efficacy, selling an herb for medicinal purposes represents both false advertising AND the risks inherent in an untested drug.

    If the active ingredient(s) have been identified, an herb is strictly inferior to a standardized, purified preparation of that active ingredient, due to variable concentration and potential effects of the other constituents.

    ONLY in the case where proper safety/efficacy testing have been done, AND no active ingredient can be identified, might it make sense to sell an herb for medicinal purposes. As a short-term stopgap while the active ingredient is identified so that it can be sold in a properly standardized and purified preparation. I am quite skeptical that this category has any meaningful extent.

  36. WilliamLawrenceUtridge says:

    While I appreciate your sympathetic tone, I suggest you stop making assumptions. You are shooting blanks. I do not see clients. I am not pretending to be a substitute doctor. I am involved in research on herbs though and am very familiar with the body of knowledge and with government regulations regarding their sale and use. Also, as I’ve said already, believing purely in historical use is not what I’m advocating. To repeat, empirical evidence is part of the pyramid of evidence, but it is the lowest level. It suggests there may be something to it, but it “needs more research”.

    Not so much assumptions as vague memory, it’s quite possible I’m remembering someone else’s comments (might be skepticalacupuncturist, I think they said they worked in a TCM “pharmacy”).

    At this point in the arc of knowledge and research, is historical use even part of the pyramid of evidence? You would probably be able to answer this question given your expertise, is it possible to look at the molecular structure of a compound and have a reasonable guess of its effects on the body?

    But I stand by my point – historical use is of questionable use even for safety information, let alone efficacy (fava beans, which I hear are delicious when paired with human livers, can kill via favism but are a significant ingredient in many cuisines). I’d sooner use it to indicate if an herb would be good in a tea than I would to prevent or treat anything. Until a specific compound is demonstrated useful in treating a condition (at which point I’d much rather consume it from a vat than a root) I see it as an ingredient, not a medicine.

    Your comment about empirical evidence is…curious to me. Even historical evidence can be seen as a type of empirical evidence, I’m assuming you mean scientific? Research?

  37. NathanAlexanderRice says:

    Just noticed this today: http://archinte.jamanetwork.com/article.aspx?articleid=1357513

    Scott: relating to your feeling on plants versus synthetic drugs, I am ok with broad spectrum standardized extracts at known concentrations, but you don’t seem to understand how difficult coming up with a synthesis is. Most molecules will have a whole host of structural isomers which can be formed which can have vastly different effects, and these are incredibly difficult to separate out in most cases. Beyond that, it is also incredibly difficult to get beyond 98% purity with synthesis/separation, and the impurities resulting from a chemical process can be quite nasty. Bottom line is that a water/oil/ethanol extraction is a safer bet every time.

    Additionally, note that pharmaceutical companies don’t WANT to just make high quality plant extracts, they want to modify it into something they can patent. Sadly, because the majority of bio-active molecules are polycyclic structures with resonance stabilization, you usually can’t do too much modification as cracking the molecule apart often can’t be done in a controlled way. Most pharma modifications of natural molecules are the replacement of a hydroxyl side chain with a bromine or iodine molecule, replacing one ester with another, or protonating/deprotonating nitrogen and oxygen atoms, as these are all fairly easy to do.

    I think if the vast majority of the institutional health care system didn’t treat people like walking piggybanks and pharmaceutical companies cared as much about people as they do shareholders and profits, you would have fewer people trying to avoid getting standard medical treatment. Don’t blame CAM because people don’t seek treatment through regular avenues, blame doctors, insurance companies, pharmaceutical companies and hospitals.

  38. The Dave says:

    The way I undersatnd it, the majority of the modifications you describe aren’t just for patenting. They are attempting to find compounds that have a larger therapeutic window, and/or fewer side effects but still have the same desired effects. But, maybe I’m not cynical enough about “Big Pharma”…

  39. Harriet Hall says:

    @ Nathan,

    “Just noticed this today:”

    You apparently didn’t notice that both Dr. Gorski and Dr. Novella have already critiqued that study here on SBM:
    http://www.sciencebasedmedicine.org/index.php/can-we-finally-just-say-that-acupuncture-is-nothing-more-than-an-elaborate-placebo/
    http://www.sciencebasedmedicine.org/index.php/an-acupuncture-meta-analysis/

  40. Harriet Hall says:

    @Nathan,

    Digitalis is a case in point. They didn’t patent Digoxin just to make money, but because the active ingredient, purified and with controlled dosage, was far more effective and safer than the herbal product. I hope you wouldn’t recommend digitalis leaf!

  41. gears says:

    I’m a little late to the party, but my favorite example of “100% pure herb” that is most definitely not pure is red yeast rice, which is lovastatin plus nephrotoxins. Mmm… nephrotoxins. Nybgrus already called BS on the “purifying them makes them more toxic” statement, but seriously, that’s poppycock. Unless you believe in magic.

    Also, I’m not a medical professional, but aren’t there plenty of instances where synergy in medication bad, because it is unpredictable? Like why, if I have pain, the doctor says, “No, don’t have some bourbon with your oxycontin because they synergize to depress your breathing,” rather than, “You’ll sure get more bang for your buck if you potentiate your opiates with alcohol.” Or other depressants, like benzodiazepines or barbiturates or whatever.

    I’m happy that I recognized everything that was wrong with Robb’s posts, even if everyone else deconstructed them before I had a chance to help. Thanks for teaching me SBM!

  42. gears says:

    @ Nathan:

    As a chemist, I have some problems with what you have said here:

    Scott: relating to your feeling on plants versus synthetic drugs, I am ok with broad spectrum standardized extracts at known concentrations, but you don’t seem to understand how difficult coming up with a synthesis is.

    It’s hard, yes, but people are capable of pretty incredible things. Have you seen how many syntheses there are of strychnine? Strychnine! That’s one hell of a molecule, and plenty of people are like, “Yo man I got this, here’s another way to make it.” Honestly, I feel like “it’s too hard” is not an adequate reason to resort to using a mixture of compounds. I can’t think of a single pharmaceutical that is used as an extract because people gave up trying to purify it.

    Most molecules will have a whole host of structural isomers which can be formed which can have vastly different effects, and these are incredibly difficult to separate out in most cases. Beyond that, it is also incredibly difficult to get beyond 98% purity with synthesis/separation, and the impurities resulting from a chemical process can be quite nasty.

    Yes, it can be difficult to separate stereoisomers, but if I said to my boss, “Hey man, these diastereomers are tough to separate, so this NMR spectrum I have here has both major and minor diastereomers,” he’d say, “That is unaccepatable you lazy sack of crap, get back to work.” And yes, impurities can be nasty, but that’s why you purify things and why we have the FDA to make sure that you did an adequate job.

    Bottom line is that a water/oil/ethanol extraction is a safer bet every time.

    No. Purifying it is better. How can you justify a mixture is safer? As an aside, extracts from plants are not always practicable, either. To use taxol as an example, even refining the active ingredient from the plant, from the bark of some yew tree in this case, was endangering the trees because stripping the bark killed them. So some clever person came up with a semisynthesis to make taxol from a compound that could be safely harvested from the leaves. There is no way that you will convince me getting a bark extract that kills the trees is better than a synthetic version of taxol. There are people with cancer who need taxol! It wouldn’t do anybody any good if the trees went extinct or there wasn’t enough to go around.

    Also, like Harriet Hall said, digitalis. There’s more than one bioactive compound in digitalis. How can you say a mixture with uncertain proportions is better that refined, pure digoxin?

    Additionally, note that pharmaceutical companies don’t WANT to just make high quality plant extracts, they want to modify it into something they can patent. Sadly, because the majority of bio-active molecules are polycyclic structures with resonance stabilization, you usually can’t do too much modification as cracking the molecule apart often can’t be done in a controlled way. Most pharma modifications of natural molecules are the replacement of a hydroxyl side chain with a bromine or iodine molecule, replacing one ester with another, or protonating/deprotonating nitrogen and oxygen atoms, as these are all fairly easy to do.

    I think I (and others) have addressed why extracts, even “high quality” ones, are inadequate. Also, I call BS on the “with resonance stabilization” comment. I don’t think that means anything in this context, it’s just a way of explaining chemical behavior. I also reject your assertion that pharma companies market natural compounds that have alcohols replaced with alkyl halides. That sounds toxic to me. Can you provide an example? Furthermore, “cracking apart” a bioactive compound would likely totally change whatever activity it once had (even if you could do it in a controlled way). In any case, processes to produce natural products can be patented, so modification may be unnecessary and is likely unproductive anyhow.

    I think if the vast majority of the institutional health care system didn’t treat people like walking piggybanks and pharmaceutical companies cared as much about people as they do shareholders and profits, you would have fewer people trying to avoid getting standard medical treatment. Don’t blame CAM because people don’t seek treatment through regular avenues, blame doctors, insurance companies, pharmaceutical companies and hospitals.

    I do not have the energy to respond to this part. I think the reality of pharmacy reflects that purified compounds are both viable to produce and better and safer to use. Anyhow, sorry for the jargon, everybody (David Gorski does it, too!).

  43. Robb says:

    nybgrus,
    It’s ironic you chose Ginkgo biloba as an example because its use of the leaf for memory does not exist in traditional use – it began with research into standardized extracts in Europe. The only traditional use was of the nut in Chinese medicine for non-memory/cognition related issues.

    Harriet,
    Digitalis is a great example of where isolating and standardizing a drug from an herb improved safety by allowing for precise dosages and avoiding toxicity. It’s more of an exception than the rule though. As far as I know, Digitalis was never used as a plant by herbalists – they used Lily of the Valley (Convallaria majalis) instead. Salix alba to acetylsalicylic acid and cannabis sativa to Marinol are some counter examples though where isolating and standardizing leads to side effects/different effects not present in the whole plant.

  44. nybgrus says:

    @NathanAlexanderRice:

    It sounds like you have learned a lot of fancy words. If only you actually knew how to apply them.

    but you don’t seem to understand how difficult coming up with a synthesis is.

    First off, non-sequiter/strawman. What does difficulty of synthesis have to do with anything about the discussion. And yes, it is difficult – that is why there are entire undergraduate and graduate degrees in it. Do you have any idea how difficult it is to launch a human being into space and return him/her safely?

    Most molecules will have a whole host of structural isomers which can be formed which can have vastly different effects, and these are incredibly difficult to separate out in most cases.

    Yes, and every med student (should) know all about enantiomers. And how difficult – yet quite possible – they are to isolate. Xopenex for example. But furthermore, one should also be eduacted enough to know that different enantiomers tend to act in an “effect – no effect” sort of way. In other words, one enantiomer has an effect on the body and the other has zero. This is due to the stereospecificity of enzymes and molecular receptors and has, simply by chance, happened to evolved a dextrarotatry chirality (aka right handedness). That is why D-glucose is what we eat and L-glucose would have no metabolic potential. It is not, as you imply, that commonly multiple enantiomers of the same molecule would have disparate effects and thus be difficult to control the effects of synthesis. And lastly, I’ll point up to my above comment – controlling chiral centers in synthetic chemistry is the name of the game.

    Beyond that, it is also incredibly difficult to get beyond 98% purity with synthesis/separation

    Really? That’s funny, because I consistently managed to get 97-99.8% purity in my synthetic chemistry courses. As an undergrad. Yes, some are much more difficult. But once again, a strawman that has nothing to do with why an herb would be more efficacious than a purified drug. Because even if it is less than 98% pure, that is still a lot more pure than an herb.

    oh wait, you’d argue:

    and the impurities resulting from a chemical process can be quite nasty.

    Which is a bollocks blanket statement. They can be. But, thanks to the FDA, they aren’t. Or, in the rare cases they are, it is known and thus a risk:benefit can actually be done to determine if the severity and prognosis of illness warrants exposure to those nasty wasty chemicals.

    Additionally, note that pharmaceutical companies don’t WANT to just make high quality plant extracts, they want to modify it into something they can patent.

    As TheDave pointed out, the vast majority of molecular modifications are to reduce side effects, increase potency, increase the therapeutic window, and favorably alter the pharmacodynamics. And that’s a good thing.

    Sadly, because the majority of bio-active molecules are polycyclic structures with resonance stabilization, you usually can’t do too much modification as cracking the molecule apart often can’t be done in a controlled way.

    Bollocks. See first comment.

    Don’t blame CAM because people don’t seek treatment through regular avenues, blame doctors, insurance companies, pharmaceutical companies and hospitals.

    The first (though only partially) correct thing you’ve said. Though for the very wrongest of reasons.

  45. nybgrus says:

    @Robb:

    It’s ironic that your only rebuttal is to pick a completely irrelevant nit. (wait, is that actually irony? It’s something anyways…)

  46. nybgrus says:

    @weing:

    Now, now. That is not true. Go to California and you can find all the marijuana you want on shelves! It is a shame they pulled coca leaves and heroin poppies from my locals Lowes Garden Center though.

  47. nybgrus says:

    @gears:

    Seems we posted at the same time. All I can say is – high five!

  48. gears says:

    @ Robb:

    I don’t want to come across as hostile, because I really do want to convince you that pharmaceutical grade compounds, regardless of source, are superior to mixtures in the form of extracts or whole herbs. So here’s trying:

    nybgrus,
    It’s ironic you chose Ginkgo biloba as an example because its use of the leaf for memory does not exist in traditional use – it began with research into standardized extracts in Europe. The only traditional use was of the nut in Chinese medicine for non-memory/cognition related issues.

    I don’t think it matters whether the use was traditional or not. A big part of this blog is how traditional modalities should not be privileged by virtue of being traditional, because it’s so easy for people to fool themselves into seeing efficacy where none exists, and that’s why clinical trials are required. Furthermore, traditional modalities that fly in the face of all evidence should be discarded without bothering to do clinical trials, like homeopathy. Others have already expressed how while there is reasonable prior probability for some herbs to have a use, unlike most of CAM, it’s still better to find an active agent and use that, which is why everyone keeps advocating for pharmocognosy over herbalism.

    Harriet,
    Digitalis is a great example of where isolating and standardizing a drug from an herb improved safety by allowing for precise dosages and avoiding toxicity. It’s more of an exception than the rule though. As far as I know, Digitalis was never used as a plant by herbalists – they used Lily of the Valley (Convallaria majalis) instead. Salix alba to acetylsalicylic acid and cannabis sativa to Marinol are some counter examples though where isolating and standardizing leads to side effects/different effects not present in the whole plant.

    Again, I disagree with you here. The rule is that isolation and standardization improve safety. It’s tempting to launch into a laundry list of pharmaceuticals derived from natural sources, but I’ll just discuss opiates for the moment. There’s a reason that people don’t use just opium or laudanum anymore, and that’s because it’s difficult to dose accurately. Furthermore, by purifying morphine and other constituents in opium, and making derivatives, you have painkillers that range in strength from codeine to heroin, novel drugs like buprenorphine, antagonists like naloxone and cool names like thebacon. That gives you such a bigger and better pharmacological toolbox than just straight opium.

    I also think your counterexamples are rather dubious. What side effects are present in aspirin and not willow bark? So far as actually using willow vs. aspirin is concerned, I can’t imagine a doctor telling someone to chew on yea-much willow bark to get the correct salicin equivalent of the (amusingly specific) dose of an 81 mg baby aspirin. There’s a reason to isolate and refine drugs.

    I’m not sure what you’re referring to with cannabis vs. marinol. Yes, I’ve heard that CBD modifies the effects of THC, and that smoking it is better for a nauseated person that trying to eat a pill. Maybe this would make it almost a legitimate exception, but even so, that’s only two compounds together, and if that’s the case then there is no reason you couldn’t find a standardized ratio and dose. Maybe you could throw them into an inhaler or something. Point is, there is nothing magical about whole herbs vs. isolated compounds.

    I will concede that I prefer the hot water extract of coffee grounds to caffeine pills.

  49. gears says:

    @ nybgrus:

    Holy crap. High five, indeed!

  50. nybgrus says:

    just goes to show the difference between knowing just enough about organic and synthetic chemistry to string a grammatically correct sentence together versus actually knowing how to do organic and synthetic chemistry. I actually almost became a chem major in undergrad until the lure of squishy science won out and I did evo-bio instead. However, along the way, I did a fair bit of chem and have the highly nerdy distinction of being the only student in my class to have succesfully synthesized – and purifed – a Grignard reagent.

    as for:

    equivalent of the (amusingly specific) dose of an 81 mg baby aspirin.

    That is because it is 25% of the previously standard 325mg pill and for a while it was easy to quarter up tabs and thus the studies were done at that level and then when efficacy was demonstrated began to be manufactured at that dosage. I think maybe kids had something to do with it as well but I’m not sure.

  51. gears says:

    However, along the way, I did a fair bit of chem and have the highly nerdy distinction of being the only student in my class to have succesfully synthesized – and purifed – a Grignard reagent.

    Awww. Give the man a beer :)

    And I almost became a biology major and have the highly nerdy distinction of being the only person I know who enjoyed studying for the MCAT.

    That is because it is 25% of the previously standard 325mg pill and for a while it was easy to quarter up tabs and thus the studies were done at that level and then when efficacy was demonstrated began to be manufactured at that dosage.

    How interesting. I’ve always wondered why that was. You learn something new everyday.

    1. Harriet Hall says:

      Off topic, but – You enjoyed studying for the MCAT? I didn’t know you were supposed to study for it. I wouldn’t even know how to start studying. I didn’t know of anyone who studied. I googled and discovered that they have MCAT prep courses now. I don’t think anything like that existed in my student days.

  52. mho says:

    I’m new to this blog and am not a scientist. Many of you have commented about Robb’s post, but I thought I could add one thing to this discussion,
    rob says “In cases of say, treating cancer, it would be crazy to rely on historical use alone, but in other examples, say you’re experiencing indigestion with gas, bloating, cramping – you’ve read that peppermint and fennel have long been used for that, there’s some small studies reinforcing the historical use, there’s a plausible mechanism of action, it’s not a life threatening condition, etc. In a case like that, why would I wait for an RCT to tell me whether I should try it or not?”

    The constellation of symptoms: bloating, urinary frequency, feeling full after eating, and pain, are more likely to occur in women with ovarian cancer than in the general population. http://www.wcn.org/articles/types_of_cancer/ovarian/symptoms/concensus_statement.html

    It seems to me that treating bloating with peppermint could easily delay cancer diagnoses.

  53. Robb says:

    gears,
    Difference between salicin in willow bark and ASA is that you don’t get the antiplatelet and stomach irritant effects from it – it’s still useful for pain and fever but not for any cardiovascular benefits. On the flip side, it doesn’t lead to gastro-intestinal bleeding. I’m sure you’re not serious about the chewing on willow bark remark, extracts standardized for salicin are available.

    Yes, CBD and THC is the synergy example I was referring to – these are just two compounds amongst hundreds. My point was simply that single molecule standardized drugs are not always inherently superior. Marijuana is one example. St. John’s Wort is another. It was long thought that hypericin was the main active ingredient. Later it was found that other constituents (hyperforin and various flavonoids) also contributed to its overall effects and were beneficial to be included in the extract. Reductionist theories are almost strangely ideological sometimes. Why is it so difficult to understand that compounds naturally found in the same plant modulate the effects of each other, sometimes in advantageous ways that single molecule drugs can’t replicate? I’m actually all for standardizing them if naturally occurring amounts are not sufficient, but the idea that there is only one possible active ingredient in a plant and that it should always be made into a drug just isn’t true in all cases.

    I think we’re coming from very different places on the isolation/standardization topic. Your examples of standardization and isolation improving safety I’d agree with because they deal with compounds that are potentially toxic and involve more life threatening conditions and uses but generally safety is not the issue in most cases with herbs, efficacy would be the reason to standardize, and then often for multiple components. In some cases, simple water extraction (aka tea) or alchohol extraction without any standardization (aka tinctures) is enough to deliver benefits.

  54. Harriet Hall says:

    @Robb,

    “you don’t get the antiplatelet and stomach irritant effects from it”

    Other sources disagree with you. For instance:

    This study showed that salicin affects platelet aggregation, although to a lesser extent than aspirin: http://www.ncbi.nlm.nih.gov/pubmed/11345689?dopt=Abstract

    “Side effects tend to be mild. However, stomach upset, ulcers and stomach bleeding are potential side effects of all compounds containing salicylates. Overdoses of willow bark may cause skin rash, stomach inflammation/irritation, nausea, vomiting, kidney inflammation, and tinnitus (ringing in the ears).”
    http://www.umm.edu/altmed/articles/willow-bark-000281.htm#ixzz27iQnnXL

    GI bleeding induced by salicin was suspected of killing a dog http://www.ncbi.nlm.nih.gov/pubmed/15526604
    And salicin was suspected of killing Beethoven. http://www.webmd.com/vitamins-supplements/ingredientmono-955-WILLOW%20BARK.aspx?activeIngredientId=955&activeIngredientName=WILLOW%20BARK

    And as for comparing single molecule standardized drugs to herbal products, you can’t go by generalizations: each case needs to be tested individually.

  55. Heh. I always have read that the reason we medicinized willow back is that it made the “aspirin” more tolerable, and decreased the GI and other side effects. To suggest that we would be better off chewing bark instead of taking precision doses is ridiculous.

  56. nybgrus says:

    Awww. Give the man a beer

    Thanks! Had one. I figured you would recognize the difficulty of the synthesis (of course, nothing even remotely difficult by your current standards, but not bad for an undergrad, eh?)

    the highly nerdy distinction of being the only person I know who enjoyed studying for the MCAT.

    I didn’t know you were supposed to study for it. I wouldn’t even know how to start studying.

    Well, I actually did not study either. I took a few practice exams about a week before I took the real thing. And I managed a 38.

    -Dr. Hall- The test has changed since the time you took it. I understand from my step-father (who is a critical care pulmonologist and graduated med in 1974) that back then it was much less involved and much more “general knowledge” than it is these days.

  57. A 38 and you went to an Australian med school? *cough* bs *cough*

  58. weing says:

    When I took the MCATs they were scored like SATs, so I wouldn’t know what 38 means.

  59. nybgrus says:

    @robb:

    Since you are such an expert, perhaps you would like to describe to us the mechanism of aspirin causing stomach irritation and GI bleeds? And perhaps differentiate that from salacin? You know, since you clearly know so much about exactly why herbals are better than pharmaceuticals, the mechanisms of actions to actually explain why should come quite easily, no?

    Why is it so difficult to understand that compounds naturally found in the same plant modulate the effects of each other, sometimes in advantageous ways that single molecule drugs can’t replicate?

    It’s not. And in fact, nobody here would disagree in principle. Merely in degree and in application. First off, most plants wouldn’t exhibit bioactive synergy and if they did it would be a negative syngergy. I mean seriously, think about it. Why – really why?? – would evolution create a selective pressure for a plant to become better and better at helping heal us? (I.e. be consumed by us?)

    But in any event, the history of the topic has shown us that, to date, the vast majority of ancillary compounds are not particularly helpful. That said, we do use synergy to our advantage in medicine. My board exams had questions which basically consisted of “Patient has [X] and is currently on drug [Y] and has [Z] lifestyle and was diagnosed with [A] – what drug should you give?” with the intent to be identification of a drug that would act in synergy with the drugs he is already on and minimizes the side effects that would most affect his life. The converse is also true – patients on multiple drugs need to be managed to be sure that synergy doesn’t make one drug act too much or too little.

    I’m actually all for standardizing them if naturally occurring amounts are not sufficient, but the idea that there is only one possible active ingredient in a plant and that it should always be made into a drug just isn’t true in all cases.

    Of course not. Straw man. But research on ancillary synergistic compounds is insanely complex. It is ongoing. In fact my own post-grad research was in – come on take a guess? – no? Herbal compounds. I designed and ran assays to test Rhodiola rosea as an anti-aging compound. With the purpose of finding all the compounds that worked to create the effect. But lets break it down here.

    1 compound to test for efficacy = 1 large complex trial.

    2 compounds to test for efficacy =2 large complex trials.

    2 compounds to test for synergy = a THIRD large complex trial

    3 compounds to test for synergy = SIX large complex trials

    4 compounds to test for synergy = 24 large complex trials*

    See how that gets out of hand quickly?

    The point being… well… lets get to another point of yours:

    Reductionist theories are almost strangely ideological sometimes.

    What does that mean? There is no ideology about saying that if you want to claim synergy between multiple compounds that the only way to verify that is to test the combinations. Nobody doubts that synergy exists. Or that herbal extracts can exhibit it. But you can’t just claim it exists for a specific combination for a specific indication willy nilly. You have to TEST it. And, as we all learned (wait, maybe it was just me?), in elementary school the more variables you add the more impossible it to test a claim. So “reductionism” as this obvious pejorative you use is indeed the only way to actually know the answer. If you just claim that 20 compounds act synergistically for a specific condition, you could run a trial. Lets say, for argument’s sake that the trial shows it absolutely works. The condition is unequivocally improved. Not even evil ol’ reductionist me would argue with you.

    Prove to me that all 20 compounds are necessary for the outcome. Prove to me that it isn’t that 10 of those compounds are actively synergistic, 5 do absolutely nothing, and 5 are just mildly harmful, adding to a total positive effect. Or prove to me that only 1 is the actual active compound, 18 do nothing, and one has really nasty side effects in just some people. And then prove to me which of the 19 compounds has that really nasty side effect in just some people. Oh, and then prove to me that the side effect is only from the single compound and not a synergistic effect from 2 (or more!!) of the remaining 19 compounds.

    Do you see the issue with it? 20 compounds have a possible 2,432,902,008,176,640,000 combinations to test. Heck, only 5 compounds need 120 trials to evaluate it.

    So no, Robb. It is not that we deny synergy exists. It is that we have very good reasons to a priori assume that it isn’t automatically tailored for us by all the random plants out there AND that to actually test out possible synergistic relationships is worthwile but takes a lot more time and information than we have. The crux is that to then simply assume that a particular set of compounds is synergistic and the most effective without unwanted side effects is ludicrous.

    So nothing ideological here. It is merely the rigorous application of tried and true, basic scientific principles.

  60. nybgrus says:

    @SH:

    It’s a fact. I can certainly appreciate your… skepticism. But if you like I can try and dig up my score and send it your way.

  61. nybgrus says:

    well said mho. I am heartened that a non-scientist can apply some basic critical thinking and come up with a very sensible view on the topic.

  62. nybgrus says:

    wow SH. Honestly, have I ever given you any reason to think I would flat out lie about something? Or to be a flat out dick towards me? I did score a 38. And yeah, I did have trouble getting into a US school. And I could just leave it at that, and move on. But just because you seem to willy nilly enjoy being a dick to absolutely anyone for any reason…

    If you think that an MCAT score alone can get you into medical school than you are a f*&#ing moron. But go right ahead and make assumptions all you want. Keep using that amazing skepticism of yours to ignore other possibilities.

  63. jmb58 says:

    Holy crap. An MCAT debate? I almost went to bed. I studied hard for it, and I did not enjoy it.

    If anyone cares, I was on a med school admission committee about 7 years ago. Back then a 38 was about 4 standard deviations above the mean (mean about 26, SD about 3). So a 38 is excellent. Now, please don’t waste your brain power in dermatology.

  64. nybgrus says:

    Indeed. I was just having a nerd-bro moment with gears. I hate to say it, but SH’s comment did get to me a bit. I have no reason to lie, or exaggerate, nor would I.

    As for me, I plan on IM followed to CC pulm. My Step 1 was a 242. Not as good as I’d hoped, but good enough. What are your thoughts skeptical? Is that number believable? I know, it is only about 2 SD’s above the mean so maybe that one actually is legit. Right?

    I mean seriously, you are a smart guy and you know your s$!t. But you really actually are an a$$shole. What was it that burned you so bad? I remember being a smoldering pile of angst and anger. It really isn’t worth it.

    I remember in the ER where I worked for 3 years before I started med school that it was oft said one should prefer an a$$hole doc who knows his s$!t than a really nice guy who is a moron.

    How about a really nice guy who knows his s$!t?

  65. weing says:

    “I mean seriously, you are a smart guy and you know your s$!t. But you really actually are an a$$shole.”

    A two finger or three?

  66. Narad says:

    Holy crap. An MCAT debate? I almost went to bed.

    Feh. Bring on the old GRE scores.

  67. Why do you keep calling me dollar signs?

    :)

  68. nybgrus says:

    Eh, probably a two. I’ve met worse.

  69. mousethatroared says:

    “I remember in the ER where I worked for 3 years before I started med school that it was oft said one should prefer an a$$hole doc who knows his s$!t than a really nice guy who is a moron.”

    This always cracks me up. I have never heard this comparison in any other field.

    It’s like saying…

    Would you rather be pulled over by a cop with PTSD who’s on steroids or a corrupt cop?

    Would you rather have a blind pilot fly your plane or one with a panic disorder?

    Would you rather have a hairstylist with advanced hand tremors or one with no sense of style?

    Would you rather the driver next to you on the freeway be drunk or nightblind?

    Really? I mean, I can see social incompetence being tolerated when a doctor is primarily working on unconscious people, but in a doctor who needs to communicate with patients to reach a diagnoses and communicate a treatment plan it seems that NOT being an assh0le should be considered a core competency requirement.

    This really must be a medical culture thing. In my experience with tech companies and military/automotive engineering, brilliant assh0les are rare…much more common are assh0les who think they are brilliant. Often behind that sh1tty personality is incompetence. And I don’t mean smart but hard to work with incompetence, I mean running your company into bankruptcy with bad decisions incompetence AND ignoring fuel system safety design flaws in school buses incompetence.

    But thanks for calling SH on his attitude. I would add that his remarks to you are only complemented by his trolling on the CFS post.

  70. jmb58 says:

    Love a good SH rant.

    “Would you rather have a blind pilot fly your plane or one with a panic disorder?”

    Not a good comparison. Imagine you are getting on a plane to Japan. Which would you rather hear from the flight attendant?

    1. The pilot is a jerk, but he is the best.

    2. The pilot is such a nice guy, but he is the worst pilot I have seen.

    That is the idea. Probably more applicable to a procedure based specialty. In reality, good people skills and communication are also very important. Doctors without them usually don’t have successful practices.

  71. jmb58 says:

    And there definitely are incompetent a-hole docs.

  72. WilliamLawrenceUtridge says:

    It always amuses me when people call out corporations for having a system that allows them to make a profit, then offers up herbal medicine as an alternative. Do all herbal doctors do this as a hobby? Because otherwise that’s quite the hypocritical double-standard for criticizing corporations for making a profit while ignoring practitioners of herbal medicine for doing the same thing. People practicing herbal medicine have just as much an invested interest and financial motive in their paradigm and approach as companies, but havea a far, far, far smaller evidence base. Corporations are generally really good at doing at least one thing – making money. Ideally that comes by selling a large amount of products people want for a low price – but not always. They’re also often good at developing new things to sell, including medicine. And many corporations do ethically, legally and morally dubious things while doing so. But please – show me a perfect solution, don’t pretend they’re unique for wanting to make a profit. And if it pisses you off that much, perhaps you might want to start some sort of campaign finance reform activism. A hell of a lot more fruitful than being a hypocrite on the internet.

  73. mousethatroared says:

    jmb58 – I’ll tell you what, how about?

    1. The pilot is such a nice guy, but he is the worst pilot I have seen.

    2. The pilot is a jerk who bickers with air traffic controllers, discounts flight attendant’s reports of suspicious activity and antagonizes his co-pilots.*

    Is the second really acceptable, because the first is worse?

    Also you said – ” In reality, good people skills and communication are also very important. Doctors without them usually don’t have successful practices.”

    I really hope this is generally true, but my assh0le reproductive endocrinologist seemed to do quite well by being the only RE available through the local HMO. So? Ultimately, I’m grateful, because it was partly his poor communication skills that helped us to decide against IVF and for adoption, so it worked out in the end, for us.

    *Actually, my brother was a commercial pilot and, yup, he’s kinda a dick, but he got along very well with his crew and generally his passengers…because he was good at his job and that was part of his job.

  74. mousethatroared says:

    Oh whoops, editing error.
    “2. The pilot is a jerk who bickers with air traffic controllers, discounts flight attendant’s reports of suspicious activity and antagonizes his co-pilots.*

    Should have read “2. He is a technically excellent pilot who bickers, etc”

    you get the drift.

  75. Robb says:

    nybgrus,
    I’ll ignore your patronizing condescension (while you are simultaneously being offended at the way someone else is commenting on you) to respond to some of your comments and questions because you do at least ask good ones. Please show me where I have once ever called myself “an expert”. It’s such a stupid term – there’s always more to learn and know. Anyway…
    ASA came about as a response to pure SA being too harsh and causing bleeding side effects. ASA is still more likely to cause GI irritation than salicin though. Salicin is like time release SA due to it needing to be metabolized – making it less effective for acute pain but longer lasting.
    Steinegger E. et al. Analytic and biologic studies on Salicaeae substances. Pharmaceutica Acta Helvetiae 1972; 47:222-234.
    As far as its mechanism of action with the byproduct of GI bleeds, I’m sure you know this already – and anyone can look up Aspirin on Wikipedia to read about it inhibiting COX-1 and 2.

    Most of your synergy comments I totally agree with. People were denying it exists though, which is why I was going into more detail about it. The reductionist ideology comment came about from people saying that single isolated compounds are always better. Maybe that wasn’t you. I agree with Harriet as well that generalizations aren’t any good here. Each plant and each synergy would have to be assessed separately. I’m sure there are all kinds of exceptions ranging from 1 isolated, standardized compound works best to multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant. As such, I retract my comment about standardization and isolation generally leading to more toxicity or side effects – it was an ill thought out generalization that has some examples (salicin vs. ASA and Marinol vs whole cannabis as far as degree of side effects) but probably isn’t true overall.

    I’ve also never said synergy should be a priori anything. I’ve said examples exist – I believe it to be relatively common amongst medicinal plants – but of course it needs to be researched before assuming anything and just to learn exactly how it works. Synergy is just an effect that can be good or bad – the specifics are everything. That’s cool that you have been researching Rhodiola – last I’ve read salidrosides and rosavin were the main actives standardized for but I’m not sure if there’s any more recent that have been discovered to also contribute to the overall effects.

  76. Harriet Hall says:

    @Robb,
    “exceptions ranging from 1 isolated, standardized compound works best to multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant.”

    It seems improbable to me that any effect could require “all” the compounds in a plant. Can you cite any examples?

  77. Robb says:

    Harriet,
    Sorry, I should clarify – I didn’t mean to imply that there are cases where “all” the compounds (hundreds or thousands in some cases) were necessary for the effect – more that the whole plant has a large number of known active ingredients and that the whole plant is sufficient to produce beneficial effects, making standardization unnecessary. By whole plant, I am not referring to eating leaves or anything that silly – but to full spectrum aqueous-alcoholic extracts. I won’t rely on the marijuana example as I’ve used it already and it isn’t even an aqueous-alcoholic extract typically. So – another example would be artichoke leaf for IBS symptoms: http://www.ncbi.nlm.nih.gov/pubmed/22363129

    Still, having said that, if there are a number of known active ingredients, manufacturers still generally test for these and select raw materials based on them being present in sufficient amounts. There’s of course a range that they would naturally occur in but it generally doesn’t fluctuate that dramatically. To use an analogy, when you eat an orange, you’re going to get a range of vitamin C, and as long as it is grown and harvested correctly, you can count on that range to be consistent. Depending on what the vitamin C in the orange is being taken for, maybe an orange is enough (preventing deficiency), or maybe you need to concentrate it more (a whole fruit extract) or maybe you need precise large amounts that research has shown work best (a standardized extract). The artichoke leaf example above is the 2nd category.

  78. Harriet Hall says:

    @Robb,

    “more that the whole plant has a large number of known active ingredients and that the whole plant is sufficient to produce beneficial effects, making standardization unnecessary.”

    I’m not sure I follow your reasoning that “makes standardization unnecessary.”
    And I’m concerned that along with the known active ingredients there might be a lot of unknown and/or untested ingredients that don’t add anything to the effect and that might even counteract the desired effect or cause adverse effects.

  79. Robb says:

    Harriet,
    Using the artichoke leaf example, it has been shown to be of benefit for IBS symptoms and hypercholesterolemia without the need to standardize specific ingredients because known active ingredients already come through in sufficient amounts with a simple aqueous-alcoholic extract. I guess you could say that this means the simple extraction process already provides some degree of standardization though. As far as unknown/untested ingredients that could cause adverse effects or counteract the effects, this is possible in some cases but not for artichoke leaf, as it has already been shown to be effective. Maybe standardizing further would produce even better results. Cost vs. gains in effectiveness becomes a factor at some point though.

  80. nybgrus says:

    @robb:

    I’ll ignore your patronizing condescension (while you are simultaneously being offended at the way someone else is commenting on you)

    Completely different. One is a case of me making a claim about myself on a forum where I have established credibility over the last 3.5 years of regular commenting as a consistent and honest person. The other is you making claims about evidence and the herbal compounds that are either entirely wrong and based in fallacies or partially wrong by over extrapolating the paucity of data on a topic to reach conclusions with significant confidence that is wholly unwarranted (i.e. coming off as an expert).

    I can’t seem to find a copy of the article you referenced to actually read. It is funny how you retract your statement about “standardization and isolation generally leading to more toxicity or side effects ” and once again cite “salicin vs. ASA and Marinol vs whole cannabis as far as degree of side effects” as the basis for your concededly incorrect over generalization, yet in your opening paragraph say “ASA came about as a response to pure SA being too harsh and causing bleeding side effects” while then asserting that salacin is still less likely to cause GI irritation. This is without cited without evidence and taken at face value belies a lack of critical though on the matter. Perhaps ASA is more likely to give you irritation but if it is less likely to make you bleed then the side effect profile has improved. Which is exactly my thesis and contradicts your own.

    People were denying it [synergy] exists though, which is why I was going into more detail about it

    Bollocks. Nobody here denied it and no doctor could possibly deny it. It is a basic and fundamental principle of pharmacology. One we use to our advantage when combining antibiotics (the old and classic example is trimethoprim and sulfamethoxazole) and the other we watch out for when combining drugs. You were fighting a straw man that whole time. And nobody here has made the claim that ” The reductionist ideology comment came about from people saying that single isolated compounds are always better. ” Your discussion on the topic lacked necessary nuance and paints the views here as all or nothing quite erroneously.

    What we do question is your assertion that “multiple standardized compounds to *gasp* the full spectrum of compounds in the whole plant” would be at all beyond infinitesimally unlikely to be better than fewer compounds. We further questions your assertion that ” I’ve said examples exist – I believe it to be relatively common amongst medicinal plants”

    For the second statement, that is quite simply and absolutely evidence free statement. There is literally nothing to support your claim that it is “common” no matter how you wish to define the word. And in fact there is heaps of evidence to demonstrate that it is quite uncommon. The fine line there is that it is indeed possible to create a synthetic drug from a plant extract which has a significantly higher side effect profile than the plant itself. Which would provide a very narrow example of the extract being “better” but certainly not best. And as we have seen, as rigorous trials of herbals are done we find the effect size to be smaller and smaller to the point of clinical insignificance. Saw Palmetto being a prime example – as the data piled up and more robust studies were done we find it has no effect beyond placebo.

    Which leads me to your first assertion. I would argue that a whole plant extract could never be better than isolates of single or just a few compounds from it. As I pointed out it makes no sense for a plant to have evolved to perfectly suit our medicinal needs. Thus, a whole plant extract will inevitably contain many completely neutral and some actively harmful compounds in varying quantities. Furthermore, biology is extremely – extremely – complex. Taking a system as complex as the human body and throwing in just ONE compound to try and achieve a positive effect is phenominally difficult and due to our current neonatal level understanding of proteomics and genomics, cannot possibly be extrapolated individually with any sort of reliability. Throwing in multiple compounds at a time, with bioactive properties we haven’t even begun to study is simply ridiculous. Claiming further that doing so is a priori better (which is exactly what you are doing since you have zero evidence to back your claim) is utterly inane.

    And that is really the point. There is zero evidence to demonstrate whole-plant synergy is useful. There is plenty of evidence to consistently demonstrate the inferiority of herbal extracts (often to the point of nil efficacy). There is a priori reason to assume that a plant would not have evolved to suit our medicinal needs. And there is every basic logical reason to know that mixing in a plethora of unkown compounds to a therapy will, on the whole, be vastly more likely to have at least a small deleterious effect than any positive one. You even realize this yourself:

    Synergy is just an effect that can be good or bad – the specifics are everything

    Yes, bad. And more likely to be bad. Which is why one cannot be truly educated on the topic and apply critical thinking and still claim that whole plant extracts are useful to be prescribed as therapy. The only exception is if efficacy has actually been shown, side effects have been demonstrated minimal, and the active molecule(s) has yet to be identified – all from the same kind of trial data that a regular drug would have to go through. Even then, it would still make sense to reduce down to the bare minimum of active compound(s) and purify them (and, as has often been shown, modify them to reduce side effect profiles and increase efficacy and improve pharmacodynamics).

    As for my Rhodiola work, that was many years ago. And it was (and still is) extremely promising. But my PI makes it a point to say that this is still very preliminary, we should not be prescribing it to everyone, and that we need to further isolate the active compounds while attempting to look for beneficial synergy.

  81. nybgrus says:

    As far as unknown/untested ingredients that could cause adverse effects or counteract the effects, this is possible in some cases but not for artichoke leaf, as it has already been shown to be effective.

    You are missing the point. Celebrex was pulled off the shelves because of an effect so small it took after market surveillance to notice it. The issue at hand is not if the extract can actually extract enough of the stuff that helps IBS. It is whether it can extract TOO MUCH as well as extracting all the other stuff that may be harmful in such a small efffect size that Phase II or III trials can’t pick it up. But if it does have an effect (which would be extremely hard to measure and find under the DSHEA) the whole thing would have to be pulled since it would be impossible to tell WHAT was actually causing the problem. And, as I explained above, the chances that out of 100′s or 1000′s of compounds in a whole herb extract that at least 1 or 2 would cause such harm is essentially gauranteed.

    Maybe standardizing further would produce even better results

    Standardizing further will ALWAYS produce better results. Because then we can know about precise dose response curves and actually have specific compounds to hunt down for signals. Pick up some $hit, throwing it against a wall, and hoping something sticks is not a good way to go about medicine.

  82. Janet says:

    @nybgrus

    SH comments didn’t seem offensive to me until I started reading your objections. I just thought he was surprised you couldn’t get into an American school with such a great score. I didn’t see anything insulting. Your interpretation was that he didn’t believe your score, but I didn’t see that at all and was startled by your reaction. Now I’m just confused.

    @SkepticalHealth

    See the above about your first entry to nybgus. Which was it?

    As to the second: Why should nybgrus be embarrassed about going to med school in Australia–or anywhere else? At least they are civilized enough to have a national health care system. I cannot imaging thinking a doctor I might see who went to an Australian medical school would be suspect in any way based on that alone. Nor can I imagine asking him why he was “dumb” enough to do so. I’ve had fabulous docs that went to med school all sorts of places–Canada, India, Philippines. Many did their residencies here and work at prestigious hospitals that I presume checked them out to some degree.

    Where did you go? Do tell.

  83. Robb says:

    nybgrus,
    I think the discussion value is probably on the wane here – or at least I’m losing interest in responding to all your points but as far as your last post, how can you equate Celebrex (a novel compound) with artichoke leaf (in our food supply for ages) as an example where “there may be harmful stuff” that small trials haven’t picked up yet? Have you looked at the statistics on deaths due to pharmaceuticals vs. those of herbs? While herbs being used since antiquity isn’t a reason to say they must be effective, it does help a lot in terms of safety. It’s a long time and throughout large populations for potentially dangerous ingredients to make themselves well known. I can assure you there are no secretly malicious ingredients in artichoke leaf waiting to be sprung on an unsuspecting public.

    So please explain how you came to the conclusion that “out of 100s or 1000′s of compounds in a whole herb extract that at least 1 or 2 would cause such harm (not sure what degree of harm you mean here) is essentially guaranteed.” That’s a strong statement. That’s a strong generalization. Surely you must have something concrete to back that up. Are you talking about 100% of herbs? 90%? What is this based on?

    Most dangerous compounds in commonly used herbs are well known by now. Take butterbur (Petasites hybridus). It contains pyrrolizidine alkaloids, concentrated in the root. Not good stuff for your liver. So extracts (clinically proven for migraines) are made using a process (super critical CO2 extraction) that ensures they don’t come along for the ride. Or strains are cultivated (the Vienna strain) that don’t contain these alkaloids. Who makes the decision that certain herbs can be grandfathered this way and certain ones are rarer and less well-known and should not be assumed as safe? That’s what the FDA, or Health Canada, or the TGA in Australia, or whatever the government authority is there for. And they completely disagree with you as far as the commonality of dangerous compounds in herbs.

  84. BillyJoe says:

    Janet,

    “Why should nybgrus be embarrassed about going to med school in Australia”

    That was my first thought. Our med schools have produced doctors who have discovered the true cause of stomach ulcers, and the first vaccine against the HPV. Is there any evidence that med schools in the USA are superior? And, yes there is our universal health care system which functions twice a well for half the cost and covers everyone without exception as well as a private healthcare system that cannot discriminate on the basis of a persons state of health.

    But SH definitely did not believe nybgrus score on the basis that he he attended an Australian medical school. I think that’s pretty clear.

  85. BillyJoe says:

    Celebrex was pulled off the shelves?
    I think you mean Vioxx.

  86. @Janet, @BJ,

    @Nybgrus is an American. No American that can get into an American medical school voluntarily goes out of country for medical school and then comes back, because it is fraught with difficulties. He will forever be classified as a foreign medical grad, and one always has to wonder why that person had to go to a whole other country just to attend medical school.

    The score that he claims to have made is higher than the average for admission to Harvard Med. Money for admissions is not an issue, because any and everybody can get student loans to pay for medical school. And I’m sure we all can tell, for as self-important and narcissistic nybgrus is (ie, as a third/fourth year med student, he acts like he’s actually doing neurosurgery, or that his decisions or notes (in charts) actually matter. Etc. He isn’t, and they don’t!), we can be damn sured if he was able to get into a remotely respectable medical school, he would, and with a score like that, he’d be welcomed into the best of the best.

    And regarding Australian schools: generally in America if you can’t get into an American medical school, you apply out of country, and common out of country places are Australia, Mexico, and the Caribbean. Some actually goto Poland as I understand, but I’m not really sure. Everybody has a reason to go there, and the vast majority of reasons are that their MCATs or grades were low, or perhaps they have a criminal record, but that would probably lead to licensing issues later down the road.

    So, for nybgrus to end up in Australia, instead of a prestigious school in America with his claimed score, he either has a huge black spot somewhere on his record, something so bad that he had to go to a whole other country for, or he lied about his MCAT score. I’ll take the simple solution and go with “liar.” Give my regards to the ECFMG.

    @Janet, where did I go? A non-prestigious state school. My MCAT score? Unimpressive.

  87. nybgrus says:

    @janet:

    from SH:

    A 38 and you went to an Australian med school? *cough* bs *cough*

    Sure, send it to nobodyscoresa38andgoestoaforeignmedicalschool@bctheywillforeverhavetojustifywhytheywentinanothercountryinsteadofarespectablestateschool.com

    So yes, clearly stating not only disbelief, but a clear pejorative of the Aussie school system, stating that a “respectable state school” would have been a better option. Even though in the latest worldwide ranking my institution ranked 33rd in life sciences and medicine in the world last year and 90th in medical schools specifically worldwide this year (which places it higher than Boston University, Texas A&M, Washington U in St. Louis, UC Irvine, Davis, Riverside, Santa Cruz, Dartmouth, Brown, Baylor, Mayo, Tufts, Purdue, Rice, Michigan State, Case Western Reserve, Colorado State, Iowa State…. need I go on?). And my clinical training is at an institution ranked in the top 5% of academic teaching hospitals in the US, with 3 NIH R01 grants, and ranked in the top 100 hospitals in the US for Stroke, GI, Critical Care, and Pulmonary Care….

    So which respectable state school did you go to SH?

  88. nybgrus says:

    @BJ: yes, I meant Vioxx.

  89. nybgrus says:

    I realized my comment I wrote just as SH was writing yet another @sshole comment is because one of my quotes of him came out as a link making three. Here it is fixed:

    @janet:
    from SH:
    A 38 and you went to an Australian med school? *cough* bs *cough*
    Sure, send it to nobodyscoresa 38andgoestoaforeignmedicalschool @ bctheywillforeverhavetojustifywhytheywentinanothercountry insteadofarespectablestateschool.com
    So yes, clearly stating not only disbelief, but a clear pejorative of the Aussie school system, stating that a “respectable state school” would have been a better option. Even though in the latest worldwide ranking my institution ranked 33rd in life sciences and medicine in the world last year and 90th in medical schools specifically worldwide this year (which places it higher than Boston University, Texas A&M, Washington U in St. Louis, UC Irvine, Davis, Riverside, Santa Cruz, Dartmouth, Brown, Baylor, Mayo, Tufts, Purdue, Rice, Michigan State, Case Western Reserve, Colorado State, Iowa State…. need I go on?). And my clinical training is at an institution ranked in the top 5% of academic teaching hospitals in the US, with 3 NIH R01 grants, and ranked in the top 100 hospitals in the US for Stroke, GI, Critical Care, and Pulmonary Care….
    So which respectable state school did you go to SH?

  90. nybgrus says:

    Argh. HTML tags: Sorry, link for references above:

    http://www.shanghairanking.com/ARWU2012.html

    http://www.topuniversities.com/university-rankings/world-university-rankings/2011/subject-rankings/life-science-biomedicine/medicine?page=1

    And as for the rest of your wonderful screed… no, I am not doing neurosurgery. And yes, I am well aware of my role and my place in the hospital. But I do manage my own patients, I have dictated their care, I see them entirely on my own and present to the attending, and my notes and orders do go in the chart countersigned by the attending/resident and make the medical record of the patient. I have come up with assessments and plans – which were implemented for patients – I have caught lab values and physical findings that the residents missed, and I even caught a vertebral crush fracture that the radiologist missed the read on. My institution expects me to be part of the team and gives me independence as I show competence. And every single review I have had for my rotations has been excellent, with most stating outright that they feel I work at the level of an intern.

    So rather than think that I am lying about my score – which yes, I am well aware is higher than Harvard’s average admissions MCAT – why don’t you consider that I am going to a vastly better medical school than you did, am getting a better education, and get your US-centric head out of your @ss for a change? I get the feeling if you were my attending you would be the only one I would write up for being a dick. And where I am training, that is a very big no-no.

    Bah. Piss off. I can’t believe I even had this conversation with you. Thankfully I know when I am an attending they will have a doctor who is smart and nice, which is way more than can be said for you.

  91. Haha! I still haven’t seen your justification for going to a whole other country for medical school. Why don’t you just admit that you lied?

  92. They’ll also have an attending that’s completely full of crap :)

    I have to admit, it’s funny seeing you so upset – all because I called you out on your pitiful MCAT lie. It makes me wonder, how much do you hate yourself if you have to lie about your credentials? (Well, you really don’t have credentials, you haven’t even finished school yet.)

  93. nybgrus says:

    @robb:

    how can you equate Celebrex (a novel compound) with artichoke leaf (in our food supply for ages) as an example where “there may be harmful stuff” that small trials haven’t picked up yet?

    Because the principle is the same. Small effects are hard to pick up, no matter where they come from.

    Have you looked at the statistics on deaths due to pharmaceuticals vs. those of herbs?

    Show me actual robust statistics for the deaths due to herbs. They don’t exist. Because there is not even remotely the same level of monitoring.

    While herbs being used since antiquity isn’t a reason to say they must be effective, it does help a lot in terms of safety.

    No, it doesn’t. Aristolochia fangchi was used in Chinese herbal medicine for a very, very long time before the very large effect of nephrotoxicity was noticed. Licorice leads to hypokalemia, hypertension, arrythmia, and edema. The list goes on. Blood letting was thought to be efficacious when in fact we know it lead to increased mortality and morbidity. The point is you simply cannot assume that something is safe because it has been used for a long time. It needs to actually be studied specifically for that – even for large effects like Aristolochia fangchi but especially for subtle effects.

    I can assure you there are no secretly malicious ingredients in artichoke leaf waiting to be sprung on an unsuspecting public.

    Really? How? You have absolutely ZERO evidence to back up that statement. Extracting the contents and ingesting it in larger quantities than would otherwise be normal has not actually been tested. And, as I pointed out above, it could actually have that effect in smaller quantities that we simply have no way of actually detecting since the effect size is so small.

    So please explain how you came to the conclusion that “out of 100s or 1000′s of compounds in a whole herb extract that at least 1 or 2 would cause such harm (not sure what degree of harm you mean here) is essentially guaranteed.” That’s a strong statement. That’s a strong generalization. Surely you must have something concrete to back that up. Are you talking about 100% of herbs? 90%? What is this based on?

    It is based on the fact that the corpus of scientific investigation has demonstrated that any given compound is more likely to do harm than good. It is MOST likely to do nothing. And yes, I mean any degree of harm – not just death or overt illness. And I am talking about 100% of anything we ingest or inhale in any way. There is simply more likelihood of harm than good. Most of the time that is absolutely minimal and/or unavoidable. And there is the interesting question of hormesis that could come into play. But in general, when you have zero evidence to demonstrate actual efficacy of something for an indication, giving it along with a slew of other compounds is playing with odds that are not in your favor.

    Most dangerous compounds in commonly used herbs are well known by now.

    That is just purely asinine. We don’t even KNOW what most compounds in commonly used herbs ARE, let alone if they are safe or not. And as I said about Aristolochia fangchi, a POTENT nephrotoxin was completely missed until 2005ish. Let alone the more subtly toxic substances.

    And then you go on to further demonstrate how purification and reduction of ancillary compounds is better… which is exactly what we have been saying here and exactly what you have been arguing against.

    Who makes the decision that certain herbs can be grandfathered this way and certain ones are rarer and less well-known and should not be assumed as safe? That’s what the FDA, or Health Canada, or the TGA in Australia, or whatever the government authority is there for.

    Nope. Those are covered by the DSHEA in the US and respectively similar laws in Canada and Oz. The regulations are shockingly lax as has been repeatedly discussed in great detail at this very blog. I suggest you educate yourself on the topic before you continue making evidence free assertions.

  94. nybgrus says:

    I didn’t lie. I have no reason to lie.

    And the program I am in is only available to US citizens and is better than any program I could have gotten into here in the US. Additionally I hold more than just a US citizenship. My fiance completed her masters in hypersonics engineering at the same Australian institution (which is #1 in the world for her type of research). And once again, if you think that merely an MCAT score can get you into school and that ONLY a HUGE black mark would prevent that with a 38, then you truly are an idiot and have no idea what you are talking about.

    As for my attendings… I have actually changed the course of management of patients because of my own assessment. I defended myself and the attending agreed and opted for my course of management. So seriously, piss off. Be a dick as much as you want – you only look like a fool for it. But for chrissake why on earth assume I would sit around and lie about anything, let alone that? Give me some time… I can’t log in to my Thx but have sent an email for my score. I am happy to settle it.

  95. Did you happen to notice the university at the top of the first list you posted? Yeah, you’re supposed score would have got in you in there. … I’m going to teach you a good life lesson. If you are going to tell a lie, at least make it believable. You could have gotten away with lying about a 31 or something, but you had to go and just be ridiculous about it.

    So, what’s your black mark that made you have to go to a sub-standard program in another country?

  96. Harriet Hall says:

    For the record, I don’t care what any commenter’s MCAT scores were or what school he went to. All that matters to me is the content of the comments, and nybgrus’s have been consistently excellent. He is obviously intelligent and well informed and he backs his assertions up with citations. If he’s this good as a medical student, I’m predicting great things for him as a doctor and advocate for science-based medicine.

    Also for the record: everyone please play nice. I’ve tried to set a good example, and I’ve asked before for commenters to abstain from personal insults.

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