Articles

One Hand Clapping

CUSTOMER: Here’s one — nine pence.
DEAD PERSON: I’m not dead!
MORTICIAN: What?
CUSTOMER: Nothing — here’s your nine pence.
DEAD PERSON: I’m not dead!
MORTICIAN: Here — he says he’s not dead!
CUSTOMER: Yes, he is.
DEAD PERSON: I’m not!
MORTICIAN: He isn’t.
CUSTOMER: Well, he will be soon, he’s very ill.
DEAD PERSON: I’m getting better!
CUSTOMER: No, you’re not — you’ll be stone dead in a moment.

Monty Python and the Holy Grail

For some unexplained reason, people at work like to tell me of the positive interactions they have had with acupuncturists and chiropractors and others of that ilk. I must have a friendly face, but I keep checking my back for a “CAM me” sign.

One of the oncology nurses was telling me how she has chronic neck pain, and that she was skeptical about acupuncture, and would never recommend these therapies for one of her cancer patients, but she went to an acupuncturist, and by gosh and by golly if her pain wasn’t better, what do you think of that Mr. Skeptic?

Call me Dr. Skeptic, I replied. Show some respect for the dead.

It does make for an awkward conversation.

I cannot deny that she isn’t better. How can I argue that she doesn’t have decreased pain? She is the one who hurts and is the one who can best judge the degree of her discomfort.

“Nope. You are not better. Sorry. Wrong. You are still in the same amount of pain you were before.”

It is an untenable position.

Then there is the issue of causality. She hurt, she had acupuncture, and immediately afterwards she hurt less. How can I say that acupuncture did not cause her pain to go down? That experience cannot be trumped by arguments that there is no biologic plausibility for acupuncture, that clinical trials show no increased efficacy compared to sham acupuncture for pain relief.

“Sorry. Randomized clinical trials prove your pain is not better.”

There is zero credibility in any argument based on the science behind acupuncture efficacy when contrasted with the the effects of the moment in the person who has less pain.

I have had similar discussions over the years with other people on similar topics, and it usually ends with the person smiling at me like I am a slightly foolish child who just doesn’t understand that they are better. The intervention was effective. The proof is in the pudding, which is why I do not eat pudding.

How can you say a patient is better?

What do you mean by better. Does it depend on that the meaning of is is?

Measuring the response to a therapeutic intervention can have two components: the objective and the subjective.

The objective part is the simpler of the two. Tumor is smaller, the patient lives longer, the blood pressure is down. Stuff you can measure. In my world of Infectious Diseases (the legitimate ID), the objective component is often cure. If the infection is eradicated, the patient is better, right? My job is simple: me find bug, me kill bug, me go home. But better is not always so simple a concept.

A recent review of daptomycin for endocarditis suggested that 37% were cured, 27% were improved and 8% failed (the remainder were not evaluable) (1). Endocarditis is 100% fatal if not cured, so what good is being improved? No much. 27% were better, just not better enough. Improved isn’t good enough if the end result is death.

I have had the occasional HIV patient who have so much toxicity from the antiretroviral medications that the treatment is worse than the disease. The medications can stop the HIV replication and improve their T cell numbers, but they feel so bad that they have preferred to go off the medications, have their HIV progress and die. Did I make them better with the medications? Is it better to live longer in misery?

To give the most extreme example, I remember a case as a fellow where a lady took a medication for her toenail fungus and it was eradicated. No toenail fungus. She was better, right? But she got hepatitis from the medication and died from liver failure. Maybe not so much better.

I can cure your infection but in the process ruin your kidneys. Are you better? It depends on the disease. If the infection would have been fatal, then it may be a good trade off. If is a minor illness, then maybe not so good.

The subjective aspects of improvement are even harder to measure accurately.

Many psychological aspects into play with the subjective improvement of patients and it may not correlate with the objective findings. It brings up the question: is the patient better if they think they are better subjectively but not objectively better?

My favorite example that illustrates the difference between subjective and objective improvement is the study that looked at saw palmetto for prostate mediated urinary obstruction. As you get older, your prostate gets bigger, and it blocks urinary flow. Patients have increased frequency of urination and a decrease in urine flow. It takes longer to empty the bladder. These are all characteristics that can be measured with urodynamic studies.

Saw palmetto was alleged to improve the symptoms of a big prostate, so it was compared with placebo in a clinical trial. It didn’t work. No big surprise, as there was really no reason to suspect that it would be effective. Its failure as a therapeutic intervention was not the interesting result of the study.

They made the placebo brown and bitter, like saw palmetto, so it would be easy for both the placebo and treatment group to think they were in the treatment group.

For the first phase of the study EVERYONE received placebo. And everyone had a significant decrease in the subjective symptoms of the enlarged prostate. No objective change however. Their urodynamics and prostate size remained unchanged.

Then patients were randomized to placebo or saw palmetto and both groups had a further small decline in their subjective symptoms followed by a gradual increase in subjective symptoms such that by the end of the year both groups were back to baseline in terms of subjective symptoms.

At the time the patients were have subjective improvements, they were having objective measurements of their prostrate: changes size of prostate and how fast they could urinate. No change at all during the trial. Neither placebo nor treatment had objective improvement in their prostate.

Patents in the study thought there were getting a therapy and responded by thinking they got better. But they didn’t get better, right? Right?

This isn’t the only example where people think they are getting improvement when they are not. Patients randomized to either sham or real acupuncture (like there is a difference) had they same duration and severity of nausea and vomiting during cancer therapy, and both groups thought use of acupuncture lead to less nausea and vomiting and wanted acupuncture again (4). Their nausea wasn’t objectively better, but subjectively it was. They weren’t better. Were they?

It is an interesting question: If people are subjectively improved but objectively the same, are they better?

I don’t know. It depends in part on what you are treating. If the patient feels better but their cancer is progressing, then no. But pain? fatigue? depression? If the patient says they are better, then I suppose they are. Even if the therapy, is as best as one can tell, worthless magical thinking. Even if they are not better, they are better. Huh?

In part, this is due to the fact that some patients will have the result that is expected of them. People will think they are better and say they are better when, perhaps, they are not better, because it is expected of them. Some patients like to please their doctors, sort of a medical Stockholm syndrome.

The most amusing example of people reporting the experience that is expected for them is in Penn and Teller’s episode of Bullshit on Magnetism, where people were told they were being treated with magnets (they weren’t) but reported feeling effects from the ‘magnets’ none the less.

The most abhorrent example of people believing they are better when they are not are those who can walk again, for however short a period of time, after a faith healing. What happens in the audience of Benny Hinn is identical to what occurs in the office of the chiropractor, naturopath, homeopath and others of that ilk. When Benny’s supplicants fall over from the power of god, they are doing what is expected of them and what they want to do. It is a giant ideomotor effect. When a patient gets better from taking magic water or having their energies aligned, the same thing is happening. They are, in part, living up to the expectations of their ‘healer’. They are behaving as is expected of them and are better even though they are not.

I suppose that instead of relying on the patient, we could rely on the practitioner. Take the interpretation of the therapeutic response of out the hands of the patients and put it into the hands of the scientist. Problem is researchers, like everyone else, may see what they want to see or what they expect to see.

The archetype of this phenomena was the N-ray debacle for the turn of the century (5).

To quote from skepdic.com, because I am too lazy to re-write it,

“In 1903, Blondlot claimed he had generated N-rays using a hot wire inside an iron tube. The rays were detected by a calcium sulfide thread that glowed slightly in the dark when the rays were refracted through a 60-degree angle prism of aluminum. According to Blondlot, a narrow stream of N-rays was refracted through the prism and produced a spectrum on a field. The N-rays were reported to be invisible, except when viewed as they hit the treated thread. Blondlot moved the thread across the gap where the N-rays were thought to come through and when the thread was illuminated it was said to be due to N-rays.”

“Robert W. Wood of Johns Hopkins University to investigate Blondlot’s discovery. Wood suspected that N-rays were a delusion. To demonstrate such, he removed the prism from the N-ray detection device, unbeknownst to Blondlot or his assistant. Without the prism, the machine couldn’t work. Yet, when Blondlot’s assistant conducted the next experiment he found N-rays.”

The N-ray’s were figments of their imagination. N-rays didn’t exist. The bias of the researcher caused them to see what really wasn’t there. That kind of pernicious and unconscious bias makes all clinical studies done by those with a financial or intellectual investment to some degree suspect. Even what appear to be objective data may have unconscious subjective bias distorting the results. When I see an article that demonstrates daptomycin is non inferior to vancomycin for staphylococcus bacteremia, I find the results a little suspect even if published in the New England Journal of Medicine, since the study was funded by the makers of daptomycin. Unlike a homeopathic study done by homeopaths, at last I know that daptomycin has efficacy against S. aureus. But I have to wonder if the medication is as effective as is purported in the study.

One wonders how much of the positive published effects of ‘alternative medicine’ are N- rays redux with a coating of patient bias. Measured effects of ‘alternative medicine’ may have all the veracity of the N-rays, and when you remove the bias and expectation, you remove the prism, and the effects disappear. I suspect most, if not all, of alternative efficacy is due to bias and expectation, since the history of these modalities is that their effects are at the edge of detection and disappear once observer and patient bias are removed. Once neither the patient nor the researcher knows whether or not they are supposed to get better, they don’t. It is one of the reasons I remain profoundly skeptical of studies of alternative therapies that show positive results. Since the underlying therapy has all the validity of N-rays, can the results, even if positive, be more than self delusion?

Bias and expectation. They make the subjective aspects of response to medical intervention difficult to evaluate. When the patient reports improvement, can I trust it? When the researcher reports improvement, can I trust it? It is part of why all studies need to be understood in context from the foundations of the basic science up to the randomized placebo controlled clinical trial. When the patient says they are better or the researcher says the patient is better, are they better? Maybe, maybe not. Being an Ockams kind of guy, if the underlying intervention has zero biologic and physical plausibility, then the results are probably due to bias and expectation. That is the simple explanation.

I wonder if bias and expectation, both by the patient and researcher, accounts for most of the so called placebo effect. For objective criteria, placebo does nothing. For subjective criteria, placebo probably does nothing as well. Patients and clinician just think they are better when they are not. And the whole of non science based medicine is built on the foundation of convincing patients and ‘healers’ that the patients are better when in fact they are not.

If this entry sounds like I can’t make up my mind, I, can’t. Determining clinical improvement is not as simple as one would like. It has been said that the mark of an educated mind is the ability to carry two contradictory thoughts simultaneously. So maybe you can say that a patient isn’t better when they are. Or they are better when they are not.

The therapeutic modalities discussed in this blog can’t work because they violate all we know of the physical world. They don’t work because they have no effect on any of the underlying pathophysiology. When bias and expectation are completely removed from the intervention, the alleged effect of the ‘alternative’ therapy vanishes like an N-ray. When patients are made better by these interventions, they are not. Right? He says nervously in the dark, wondering if he is talking only to himself.

‘Alternative’ modalities will probably continue to persist no matter what science based medicine discovers. The fact that they are based on nonsense and are not effective will not prevent them from being perceived as effective. And if you think you are better, even if it is based on a lie, are you not better? The ethics of fooling yourself and your patients will probably be the topic of a future entry.

It is not as easy as one would like to determine if an intervention really, truly, honest to goodness makes someone better. It is why my conversation with the nurse was unconvincing for both of us. She perceives causality and improvement. She is better. I perceive bias and self-delusion. I know she is not better. Even though she is.

For now I will ask the question again. Its like a zen koan: if a tree falls in the forrest and there is no one to hear it does it make a sound? (Well, no, it doesn’t (3)). If the patient thinks they are better with a therapy when objectively they are not, are they better?

—————————————————————————————————————

(1) Daptomycin in the treatment of patients with infective endocarditis: experience from a registry. Am J Med. 2007 Oct;120(10 Suppl 1):S28-33.

(2) Saw Palmetto for Benign Prostatic Hyperplasia. N Engl J Med 2006;354:557-66.

(3) The answer is no, it doesn’t not make a sound. This was definitely proven in an experiment by Bob and Ray over 40 years ago.

(4) http://www.sciencedaily.com/releases/2007/09/070926100551.htm

(5) http://skepdic.com/blondlot.html

Posted in: Science and Medicine

Leave a Comment (39) ↓

39 thoughts on “One Hand Clapping

  1. apteryx says:

    You say: “Once neither the patient nor the researcher knows whether or not they are supposed to get better, they don’t. It is one of the reasons I remain profoundly skeptical of studies of alternative therapies that show positive results.” Doesn’t the first sentence describe the standard randomized placebo-controlled trial? Yet you “remain profoundly skeptical” of randomized placebo-controlled studies of CAM, if they show positive results.

    Evidence: You say, of one recent saw palmetto trial that was negative: “No big surprise, as there was really no reason to suspect that it would be effective.” None? Look up “saw palmetto Cochrane” on PubMed and you will find a 2002 Cochrane review based on 21 randomized trials involving 3139 men. 18 studies were double-blind, and allocation concealment was demonstrated to be adequate in 11 of those. Conclusions were that saw palmetto produced significantly greater symptomatic improvement than placebo and similar improvement to finasteride (which is both much more toxic, and more expensive). Many of these studies also observed increases in flow rate. Long-term efficacy is not known; it might be that finasteride would be much better over a period of several years, although there is no evidence of that.

    Now, you may want to argue that one negative study outweighs all of these. Still, if before that negative study was done there had already been almost two dozen studies – no doubt more since 2002 – that were overwhelmingly positive, and you still say there had been no reason even to suspect that it might have any value, it suggests that you either are not familiar with the literature or you are not evaluating it objectively.

    Where botanicals are concerned, one reason people use them is that they are often less potent than drugs – which does not equal worthless – but they are concomitantly a lot safer. You laudably acknowledge the case you saw of a woman who died to get rid of toenail fungus, which was usually not seen as a major health problem before drug companies set out to exacerbate social fears relating to it. You can also treat toenail fungus with topical tea tree oil. The rate of complete cure is significantly lower than with oral fungicides. However, there is zero chance that you will end up dying or having your liver hacked out and replaced because you used it. Would it perhaps have been better if this woman, and other patients taking the same dangerous drug, tried tea tree oil first?

  2. weing says:

    Speaking of natural remedies. Wasn’t there a study a few years ago that showed men had less toe fungus if they urinated while taking a shower? Sounds cheaper than tea tree oil.

  3. ellazimm says:

    If a tree falls in the forest and there was no one there to hear it . . .

    How do you know it fell?

  4. Fifi says:

    apteryx – “Where botanicals are concerned, one reason people use them is that they are often less potent than drugs – which does not equal worthless – but they are concomitantly a lot safer.”

    By botanicals I’m going to assume you mean directly consuming plants as medicine? Just exactly how is a substance with varying, unknown degrees of potency safer than taking a substance with a known potency that has been researched to understand which potency is the most effective? The wildly varying potency would seem to hinder both efficacy and knowing what potency is safe. And how are botanicals not drugs? They may not be pharmaceuticals but they are drugs if they have medicinal properties. Once they’re made into tinctures and such they’re also no longer in their natural state. Certainly people perceive naturally occurring substances to be “safer” but that perception is based upon ignorant and rather romantic ideas about nature not the reality of the natural world or plants. Quite odd ideas really considering how natural death is and how poison plants exist naturally all over the world – one can only conclude people who hold these ideas don’t get out in nature much.

    apteryx – “You can also treat toenail fungus with topical tea tree oil. The rate of complete cure is significantly lower than with oral fungicides. However, there is zero chance that you will end up dying or having your liver hacked out and replaced because you used it. Would it perhaps have been better if this woman, and other patients taking the same dangerous drug, tried tea tree oil first?”

    I guess you’re not aware that it’s possible that tea tree oil (and lavender oil) have some rather unwelcome side effects when used on young boys and are suspected of potentially being endocrine disruptors and androgen inhibitors? So not only is tea tree oil less effective, it’s got its own set of potential side effects that haven’t been properly studied yet.

  5. Joe says:

    Terra Sig had an interesting take on the Saw Palmetto study http://scienceblogs.com/terrasig/2007/07/another_botanical_clinical_tri.php
    In brief, for most herbs, the active ingredient is unknown (if it even exits). Therefore, one cannot know that the clinical study used appropriate doses.

    Speaking for myself (not Terra Sig), when I have looked at literature on herbs- the components on which herbs are chemically standardized have been arbitrarily chosen. They are compounds that are characteristic of and/or abundant in the plant, that are simply assumed to be active. Aside from the irrational assignment of activity, it begs the question that there is any activity.

    You wrote “Where botanicals are concerned, one reason people use them is that they are often less potent than drugs – which does not equal worthless – but they are concomitantly a lot safer.” I am not sure we know they are safer. For example, there are many cases where herbs are contaminated, and that is really difficult to find.

    If you give me a sample of a drug, I can tell you quickly if it is likely to be the claimed substance, and a little while later I can tell you how pure it is. If you hand me a sample of “tinselweed” (some green-brown-gray flakes), I might be able to find a characteristic compound that makes it likely it is labeled correctly. However, the weed is a gmisch of thousands of compounds, and I cannot reasonably check for the millions of others that don’t belong.

    There are herbs that cause problems with a long induction period. Auristolochic acid ( in aristolochia) causes kidney failure over the long term; then, if the victim survives via a transplant, the residual kidney is likely to become cancerous. Traditional herbalists cannot detect that sort of problem. Perversely, although we now know about that, we keep finding mislabeled herbs contaminated with aristolochia, with dire consequences.

    Do not misunderstand, I found this post fascinating; and I think there are many valuable natural products waiting to be discovered.

  6. DavidCT says:

    I agree with Fifi. Herbs and botanicals are being used as drugs. Unlike the situation with drugs many of the people suggesting them have nothing but woo-woo training as herbalists. The late Barry Byerstein (sp?) had his graduate students go to pharmacies selling herbal meds and they found the information given to be unreliable.

    There is also the matter of what is in the preparations sold as herbs. How much active ingredient and how much powdered camel dung filler. OOPS! they are from China – I should have said Powdered Panda poo and lead.

    The point is just how safe are “natural” products when you cannot always know what they contain and the people advising their use have been shown to be very inconsistent in their knowledge.

    Of course if you feel better they must work!

  7. daedalus2u says:

    Urine is a good source of ammonia (from hydrolyzed urea). If you have a resident biofilm of ammonia oxidizing bacteria, supplying ammonia to it will enhance its activity and supply increased NO/NOx. Acidified nitrite is curative of tinea pedis. The normal pH of the skin is 4, low enough for nitrite to disproportionate into NO and NO2 and have good antifungal and antibacterial activity.

    http://www.ncbi.nlm.nih.gov/pubmed/9555794

    NO/NOx suppresses the quorum sensing that causes expression of virulence factors and inhibits formation of bacterial biofilms (such as Pseudomonas and Staphylococcus). NO/NOx is also a good vasodilator and so is likely protective against peripheral diabetic neuropathy.

    Virtually all natural water sources have ammonia oxidizing bacteria in them. Municipal water purification can remove them, but they are more resistant to chlorine than are coliforms. When chloramine is used as a disinfectant the ammonia decomposition product nourishes them and populations in chloramine treated water systems can get very high. They don’t show up on any standard water microbiological tests so their presence is mostly unrecognized.

  8. Joe says:

    @apteryx – “You can also treat toenail fungus with topical tea tree oil. The rate of complete cure is significantly lower than with oral fungicides. However, there is zero chance that you will end up dying or having your liver hacked out and replaced because you used it. Would it perhaps have been better if this woman, and other patients taking the same dangerous drug, tried tea tree oil first?”

    Where is this evidence that there is zero chance of dying or developing liver disease? Never mind, I know- the evidence does not exist; and, as Fifi observed, those are not the only concerns.

  9. Fredeliot2 says:

    If a man says something and no one is around to hear him, is he still wrong?

  10. apteryx says:

    weing – I can’t find the urine study on PubMed, despite searching multiple sets of terms. But hey, peeing in the shower is harmless, so if you feel it might confer a health benefit, go right ahead.

    Fifi – There is an assumption sometimes that people who use botanicals believe all plant species are safe for internal use by lay people. This would indeed be “ignorant… romantic… odd…” and reflecting a lack of contact with nature. However, it is what is (properly!) termed a straw man argument. Nobody believes that. Everyone admits that there are poisonous plants in nature, and they do not casually consume jimsonweed leaves. But there are also non-poisonous plants in nature, as evidenced by the fact that we and our ancestors have eaten plants for many millions of years.

    It is certainly possible for a plant that seems harmless in occasional use to have hidden long-term toxicity (as is the case for the now-banned Aristolochia). However, if we know of hundreds or thousands of people who have wound up in liver failure from acetaminophen, and not a single person who has died of liver failure from eating tomatoes, we can rationally conclude that tomatoes are probably safer for your liver than Tylenol. The fact that tomatoes, like all plants, are chemically variable is irrelevant, because the therapeutic dose range is so broad. That is, even the most potent tomato does not provide a dangerous level of any of the potential toxins it contains, and the chemical variability is genetically constrained: no tomato will suddenly turn up with a toxic level of hyoscyamine.

    As for the “unwelcome side effects [of tea tree oil] when used on young boys,” you’ve been scammed by a group of MDs with an axe to grind (Henley et al. NEJM 2007;356:479-85). They reported three cases of prepubertal breast enlargement in boys who had used shampoos, etc. containing lavender oil. They proceeded to assume and assert that the lavender oil was to blame. In one of these cases, the product also contained a small amount of tea tree oil.

    If lavender oil is already guilty, why assume that the tea tree oil was guilty too? They did a little cell-culture assay in which both oils showed weak estrogenic effects – at 600,000 to 1.4 million times the concentration of the positive control, estradiol. Perhaps all essential oils would show the same results in that assay. Perhaps every product in the children’s houses that contained compounds leached out of plastic would have done the same. They did not test such products, so we don’t know. Such assays produce a huge number of false positives, because they do not tell us anything about activities in complex living organisms at the far tinier concentrations that could actually be absorbed by, e.g., washing the hands with lavender soap. (Most compounds in tea tree oil are not absorbed well through the skin.)

    Incidentally, two of their three “patients” were hormonally normal, whereas one had high testosterone levels, which even they don’t allege can be caused by lavender. If I recall correctly, they accepted as fact the completely unverified opinion of one mother that her young child’s breast size varied by time of day, and connected that to daily exacerbation and resolution related to daily use of the shampoo. Yet they also considered the resolution of these cases, *months* after the products were discontinued, to be proof of causality. Well, how long does it take a breast to shrink? The truth is, as I understand it, that breast enlargement in boys is not uncommon and often goes away over time. How many boys with harmless gynecomastia had they seen in their careers who did not use lavender soap or shampoo, who had to be sifted through and discarded to find a few who had been “exposed” to botanical products? How does that ratio compare to the percentage of normal children who use products that contain a few drops of botanical oils, which are extremely common? In short, these guys twisted the facts to support their pre-existing opinions.

  11. pmoran says:

    Mark highlights THE major barrier to communication between skeptics and believers.

    The most obvious explanation for such a widespread and often impressive human phenomenon, when looked at in the light of known human suggestibility, and the availability of numerous other possible mechanisms ranging from altered levels of attentiveness to symptoms having “done something” about them to the release of neurotransmitters by placebos, is that some of these these persons *are* better, and not merely saying so, for having resorted to placebo-type medicine (others would, of course, have just got better anyway).

    It would also be an extremely useful evolutionary trait over the previous hundreds of thousands of years of human existence. It is profoundly plausible.

    The Kaptchuk article recently discussed here by Steve Novella also suggests that the benefits can under some circumstances rival those of effective medications.

    I know this is controversial, and uncomfortable for skeptics and most medical scientists to contemplate, but it is at minimum a possibility that cannot be fully discounted on the available evidence. This skeptic would love to be convinced otherwise. I think science-based medicine can create room for such a possibility. It could help public dialogue.

  12. Thanks Joe for the link on the Saw Palmetto study: http://scienceblogs.com/terrasig/2007/07/another_botanical_clinical_tri.php
    Apteryx, I’d be very interested in your comments on it.

    You stated, “The fact that tomatoes, like all plants, are chemically variable is irrelevant, because the therapeutic dose range is so broad.”

    Do you distinguish between botanical drugs and food plants, between pharmacologically active ingredients and nutrients?

    Do you know of any evidence demonstrating that the cultivated tomatoes most people eat contain any significant amount of pharmacologically active ingredients?

    Do you think that years of cultivation may have standardized food plants to a much higher degree than can be found in uncultivated medicinal herbs?

  13. daedalus2u says:

    Direct estrogenic effects are not the only mechanism for gynecomastia. Inhibition (or induction) of different cytochrome P450 enzymes can also affect steroid physiology. Many terpinoid compounds are metabolized via the cytochrome P450 enzymes.

    Blood levels are not necessarily the relevant tissue compartment. Many steroids are autocrine and paracrine regulatory molecules. Absorption through the skin of the scalp may lead to higher doses in the brain due to flow through the emissary veins.

    PM, I completely agree about placebos. I see it as the neurogenic triggering of “something”. Certainly organisms that can neurogenically trigger “something” that makes them get better will out compete organisms that can’t trigger the same “something”.
    You don’t want to trigger the “something” unless you actually need it, so it is plausible that the “trigger” would be something elaborate and perhaps learned. A mother’s kiss perhaps would be the archetypal placebo.

  14. apteryx says:

    rjstan – The opinion you link to correctly states that the material in this study was inadequately characterized, as were test materials in several other NCCAM-funded studies. Results from a test of a lousy product are not applicable to the whole species. I don’t know why NCCAM did not think of that before wasting millions of dollars. Beta-sitosterol has been used as a marker compound for saw palmetto and is also present in several other plants that have been successfully used to alleviate BPH symptoms (e.g., pygeum, pumpkin seed). I would have thought that a minimum level of beta-sitosterol should have been absolutely required.

    Do I distinguish between medicinal plants and food plants? Only as a grade, not as two separate categories, because plenty of plants – from ginger to fennel to burdock – are used for both, while some are used only as food and some only as medicine. We are told that eating tomato products may reduce the risk of prostate cancer, maybe or maybe not due to the lycopene content. If true, that is certainly a medicinal effect, as lycopene is not an essential nutrient.

    Yes, the corporate cultivated vegetables you get at your supermarket are fairly standardized, but if you garden using heirloom seeds or study traditional landraces, you will see much more variability within species. Cultivation can either reduce the variability of the wild species (by selecting only the most productive or tastiest variants) or increase it (by breeding and preserving interesting new forms and flavors, as in pepper and mint cultivars). But agriculture itself is a fairly recent innovation; for almost all of our evolutionary history, we ate only wild plants. These are typically variable, but again, it’s always within limits. Individuals may have more or less of their natural secondary compounds, but they are not suddenly going to start generating poisons never before seen in the species. Some plants are both toxic and variable enough that if you get an unexpectedly potent plant, you could accidentally consume a toxic rather than beneficial dose; foxglove is a good example. We have a pretty good idea, based on millennia of observations, of which plants those are, and treat them with caution; in current Western practice, use of such plants is seldom tolerated at all.

  15. Apteryx, the article Joe linked to also stated, “The scientific approach would be, minimally, to design an in vitro model for markers of prostatic hypertrophy (not exactly my area of expertise) and then chemically fractionate saw palmetto extracts to find the one, two, or ten chemical compounds that had effects on these endpoints. Then, you might want to try some simple metabolism experiments (and perhaps a phase I clinical trial where these pharmacokinetic parameters are assessed before anyone in their right mind would jump full bore into a phase III efficacy trial) to be sure that any of these compounds might make it to bloodstream and the prostate in concentrations consistent with these effects when patients are given a certain dose. After all, we catabolize fatty acids for energy and the liver’s cytochrome P450 drug metabolizing enzymes are likely to have first evolved to destroy plant sterols we encounter in our diet.”
    What is your opinion about that?

    I do not have the time to investigate saw palmetto, to pull and read all the relevant literature. However, based on the link and your statements, I would conclude that the studies done to date have been on specific products rather than the specific botanical. Do you agree that is correct?

  16. apteryx says:

    I do not agree that we should refuse to study in vivo effects of plants whose active components have not been identified. That can be extremely difficult in practice. More research is now showing that compounds in plants may interact synergistically – either because there are lots of compounds with similar bioactivities, or because one compound may enormously increase the bioavailability of another. In the latter case, a bioassay will identify the former compound as inert, whereas it is actually essential. It’s valuable to know how things work, if you can figure it out, but when things are now in use (and have been for millennia), what the users want to know right now is how well do they work?

    The essay demanded that, before a trial of efficacy was done, active compounds be identified that would be absorbed and transmitted unchanged to the prostate in doses that were active in a bioassay. This is nonsense. Compounds may be active in vivo by mechanisms we do not see in our crude bioassays, thus may work at either higher or lower concentrations than we expect. Very often, it will not be the originally consumed compound that is active but one of its metabolites in the body; if it were found sitting unchanged in the plasma for hours, that would prevent it from working. For that matter, even a compound that is not absorbed into the body at all can have medicinal properties through effects in the digestive tract, e.g. on intestinal flora or on immune cells there. If there is already evidence from human use and animal studies that something works, an honest researcher will not deny that possibility simply because it hasn’t been demonstrated to work by a mechanism simple enough to be easily elucidated.

    Generally speaking, you should have a Phase 1 dose-response study before you jump into a very costly Phase 2 trial with no idea whether you are using the right dose. However, if there are already a lot of smaller human studies that are telling you such-and-such a dose is effective, that’s reason enough to use that dose.

    As you say, all studies are done using a specific batch of material, rather than “a species” as a whole. It is not always easy to know how well the results apply to other products. The results of the many studies of ginkgo biloba standardized extract EGb 761 cannot be offered as proof that your homemade ginkgo tincture is safe and effective, because it has significantly different chemical content. If there are a dozen studies of a botanical using patients with similar conditions, and results are variable, it could be because some of the studies used poorer material that did not give an adequate dose. (This can be done accidentally or with full knowledge: one of the recent echinacea studies glorified by the media used material totally lacking in a required active marker compound.) That’s why it is important for researchers to chemically characterize their material as well as possible, so the reasons behind those contradictory results can be sorted out as data accumulate.

    The trouble is that the anti-herb lobby will often claim positive results from a botanical study apply to no other product – or even no other batch! – because plants are supposedly so very variable that no two products are similar enough to have similar activities. And indeed positive results don’t imply that every product using the same species will be effective, because there are always lesser-quality products. But when there is a negative result, the same people will use the test product as a synecdoche for the entire species. “That batch of echinacea didn’t work? That proves that the species is worthless!” This is disingenuous.

  17. Joe says:

    @apt you wrote “More research is now showing that compounds in plants may interact synergistically – either because there are lots of compounds with similar bioactivities, or because one compound may enormously increase the bioavailability of another.” Evidence?

    @apt you wrote “In the latter case, a bioassay will identify the former compound as inert, whereas it is actually essential.” We have been through this before, natural products chemists know how to deal with this.

    @apt you wrote “It’s valuable to know how things work, if you can figure it out, but when things are now in use (and have been for millennia), what the users want to know right now is how well do they work?” We have been through this, more than 100 inactive herbs were being used (for millennia) against malaria in China.

    @apt you wrote “Compounds may be active in vivo by mechanisms we do not see in our crude bioassays …” True! However, considering that one needs 100 subjects for a clinical trial to rise above the level of anecdote (in most cases), human trials are impossibly expensive for use in screening herbs. In addition, (I repeat) without knowing the active ingredient, one cannot claim that a negative study is definitive. You may wish these things are not true; but they are.

    @apt you wrote “Very often, it will not be the originally consumed compound that is active but one of its metabolites in the body …” How often? Evidence. Just as your references to “synergy” require proof, you references to “prodrugs” require proof.

  18. Harriet Hall says:

    “compounds in plants may interact synergistically”

    Compounds in plants may also counteract each other. What are the odds?

  19. apteryx says:

    Sorry, Joe, I am not here to do your looking up for you. That has proven to be a waste of time. The statements that a plant can have multiple active compounds, or that pharmacokinetic synergy can occur, or that metabolites of either natural or synthetic compounds may be active in the body, are not controversial among people who have any familiarity with the literature. If any other reader is interested, they can say so and I can suggest a few search terms by which they can locate examples in PubMed.

    To correct a few of your other misapprehensions, nobody has yet shown that 100 – or is it 200 this week, or 199? – herbs that were genuinely inactive in clinical practice were “used for malaria for millennia in China.” As you might put it: “Evidence?” Please don’t bother to cite that same completely uninformative abstract that says only that A. annua was the best plant according to a particular screening method. And while a clinical trial with fewer than 100 participants is not the last word on the subject, it is also not an “anecdote”; that’s what statistics are for, which is why small studies on conventional medicine are treated as being science.

  20. apteryx says:

    Harriet – Who knows? I don’t dispute that it is possible to get a single-compound drug out of a plant that is not effective as a botanical, either because of interference from other compounds or just because the compound is present in very small quantity. But it is also possible to have an effective botanical that cannot readily be made into a single-compound drug. For example, hypericin is one of the active compounds in St. John’s wort, even though hypericin alone is not very effective; it turns out that the presence of flavonoid compounds in the plant significantly increases bioavailability. Hypericin in the plant extract is therefore “better” than hypericin in a pill would be.

    If a plant is used successfully by humans, and it is shown to be effective by human studies – and generally also animal studies – why, then, we know that whatever combination of compounds it contains must manage to be bioactive. Is it possible that finer fractionation and reduction to one or two compounds could make a more potent product – measured in terms of equal mass of that compound! – without a reduction in safety? Sure, maybe. But maybe not. For any particular plant, that remains to be demonstrated. Until and unless that is done, a plant that has been scientifically demonstrated to be safe and effective is an eminently rational consumer choice.

  21. Joe says:

    @apt, don’t be sorry; inability to support claims is normal for quacks. I have seen a lot of it, it was expected of you.

    apt wrote “Please don’t bother to cite that same completely uninformative abstract that says only that A. annua was the best plant according to a particular screening method.” If you recall, I directed you to the full-text article. Funny, you could not see it in the ref to the abstract “Free Full Text Available” on the page. Maybe you can cite evidence that others were worthwhile; I won’t hold my breath.

    Apt wrote “And while a clinical trial with fewer than 100 participants is not the last word on the subject, it is also not an “anecdote” …” Evidence? Where do you draw the line?

  22. apteryx says:

    Joe – I clearly will never alter your opinion on any subject, nor will you alter mine. Therefore, if there is any purpose in our responding to or past one another, it is to convince undecided readers that there may be some truth to our opinions. We are both anonymous readers here, not named experts whose opinions may be thought to have special value. We can only appeal to others by making them aware of facts, logic, or common sense that might support our opinions. I refrain from calling you names, insulting your intelligence, and nitpicking over irrelevant minutiae in your messages not because I am fond of you, but because I think other readers would be turned off and assume that I had no facts or sense to offer. Now, I am baffled by your frequent resort to ad hominems. There are arguments to be made against botanicals – though ludicrous ones, when applied to the entire plant kingdom without exception – or commercial botanical products. Why don’t you use those, as surely they would look like a better case to others?

    Don’t waste your time demanding “Evidence?” from me anymore either. Again, neither of us is an expert with every reference at their fingertips. I have previously spent time looking up, cutting and pasting a whole list of PubMed citations to post here, only to have you sneer about having received an “infodump” and refuse to address the facts in the abstracts. I will never again waste time out of my workday doing online research at your demand, when I know that you don’t really want to see the results or you’d be able to do it just as easily yourself. If someone else asked who was not familiar with PubMed, I’d consider it.

    (For the reader who still cares about the antimalarials issue, if there are any: yep, I overlooked the “free text” button on an abstract page once and had to have it pointed out to me; I must be a real moron. But when you look at the full text, it doesn’t support Joe’s extremely unlikely claim either.)

  23. Apteryx you said, “I do not agree that we should refuse to study in vivo effects of plants whose active components have not been identified.”

    If a way can be found to standardize the plants, I accept that. However, I strongly believe that it is the people who sell them as supplements who must standardize the raw material and do the required studies and I think that a distinction must be made between “whole plants” and extracts and pills made from them. Any studies with whole plants will have to be repeated with the product packaged and sold as a supplement and results will have to be consistently replicated. In othe words a body of evidence rather than a few studies will be required.

    I will go even further. There is a world of difference between an individual brewing an herbal tea with plants for personal consumption and a company manufacturing a dietary supplement from plants for sale in the commercial market. Without good studies which have been consistently replicated on a standardized product it is impossible for a supplement manufacturer to know that his product is either safe or efficacious for anything. Yet supplement companies sell products that they have neither standardized nor studied adequately all the time and can do it legally. In this day and age it is incredible that they can get away with that and even worse that the general public doesn’t know it.

    If you have evidence demonstrating that specific plants work synergistically, I would most definitely like a search term. That being said, I do not expect to have the time any time soon to actually investigate the topic. To do that I will have to order and read the relevant articles. I learned long ago not to rely on abstracts alone. Also, I am told by people who are experts that PubMed is not the best source of drug studies and would assume that is true for botanical drugs as well.

    You seem to have a lot of knowledge about food plants. I do not, but I find it strange that you keep repeating that there are plants now in use that have been in use “for millennia”. Do you really believe that the St. John’s Wort picked as a weed today is the same as the one picked 500 years ago?

    I know very little about plants, gardening or nutrition. However, I do have some knowledge and experience with “natural dyes”. I suspect that we can learn more about botanical drugs from dye plants than from food plants. With dye plants there is great variations in nature. The color they produce when you hold all else constant is your control. I have written articles on this that are posted on my webpage, but they were written for the general public not scientists as are on this forum.

  24. Fifi says:

    Apteryx – Well, actually, you were claiming that “botanicals” are safer than pharmaceuticals. Or that there is an (incorrect) public perception that “botanicals” are inherently safer than pharmaceuticals, that you’re continuing to promote. Just to remind you….

    apteryx – “Where botanicals are concerned, one reason people use them is that they are often less potent than drugs – which does not equal worthless – but they are concomitantly a lot safer.”

    I merely pointed out the obvious fact that plants (“botanicals”) can also be poisonous and are not inherently safer. I’m glad you agree since you were originally promoting an erroneous idea regarding safety that potentially puts people at risk and perpetuates ignorance. Are you trained as some form of a healer and/or do you recommend “botanical” drugs to people who consider you to be an expert? I’d hope you’d feel ethically responsible for not promoting dangerous ideas you know to be untrue.

    As for why they tested tea tree oil, I’d suspect this has more to do with the study being done in Australia where tea tree oil originates from (and is big business and in lots of products). It is, of course, always possible that these boys’ symptoms were investigated because the doctors in question have an deep seated, obsessive vendetta against lavender and tea tree oil but that hardly seems like the most likely reason. Or they could genuinely care about their patients and noticed something worth investigating scientifically because, unlike non-science based people who consider themselves healers, they don’t assume that their subjective observation and personal conclusions count as science or “proof”. Clearly more studies have to be done but in the meantime caution seems warranted when using these kinds of products on boys, just as it is with any potentially unhealthy chemicals used in skin and hair products. Incidentally, tea tree oil is potentially lethal to cats (just in case anyone is foolish enough to believe natural=safe).

  25. apteryx says:

    There seems to be no point in continuing this argument. (Fifi, you might see my response to Joe above.) Dr. Crislip’s original post asked some very interesting questions, which have not been discussed as much as they deserve. (For example, what is the implication of the fact that the benefits of conventional medical treatments are also partly due to “placebo effects”?) I wanted to correct his error regarding saw palmetto, but did not intend that to turn into a lengthy argument regarding herbs (one of the “CAM modalities” most likely to have non-placebo benefits) that would crowd out discussion of the main subject.

  26. Apteryx, I am really trying hard to get facts not opinions. I am trying very hard not to argue, and since you seem to want to educate, I do hope that you will respond to the comments I made above about things like whether or not you believe a botanical used today really is the same as one use 500 years ago, whether or not you see a difference between an individual preparing an herbal tea for personal use and a manufacturer producing liquid extracts and pills from the same herb for the commercial market and whether or not in the second case you believe that there is a need to study not only the botanical but also the product manufactured from it. I really doubt that Dr. Crislip will mind.

    You said to Joe, “We are both anonymous readers here, not named experts whose opinions may be thought to have special value.”…”I have previously spent time looking up, cutting and pasting a whole list of PubMed citations to post here, only to have you sneer about having received an ‘infodump’ and refuse to address the facts in the abstracts.”

    From reading your posts I got the impression that you most definitely do consider yourself an expert on botanical drugs used in traditional healing and I thought that you actually had access to and had read the articles you cited. I thought you had mentioned subscribing to the natrual products (if that is the correct name) data base.

    The only thing I am an expert on is silver drugs and supplements and I assure you that I have located and read practically everything on the topic in the English medical literature a lot of which does not come up in PubMed. As a result of that experience, I have a very dim view of learning much from abstracts. People often send me abstracts that they have cut and pasted. Most of them have never read the articles and I know, because I have, that they do not support the conclusions the sender has drawn.

    You said to Fifi, “There is an assumption sometimes that people who use botanicals believe all plant species are safe for internal use by lay people. This would indeed be ‘ignorant… romantic… odd…’ and reflecting a lack of contact with nature. However, it is what is (properly!) termed a straw man argument. Nobody believes that.”

    That indicates to me that you are not familiar with the alt market place that the rest of us find so disturbing. “Natural is safe,” is the marketing slogan that launched the dietary supplement industry into the billion $$$ one it is today. Several years ago alt. promotional material like brochures, books, magazines and Internet forums were full of that line and the general public fell for it hook, line and sinker. It took years to make the majority of them realize on a conscious level what they already knew. Some natural things, including some plants, are deadly. While not as blatant today, the mystic of “natural” still sells product and you can bet that the salesmen know it. I am so sick of seeing “natural” on food containers. I’m tempted to ask the grocer where he keeps the unnatural raisins because I’m tired of the natural ones.

    The sister slogan to, Natural is safe, is, Synthetic is dangerous, which still feeds very nicely into the chemical phobias the general public has even after realizing that not everything “natural” is good, and if you read alt. med. lit. (aka promotional material) you will see that they encourage chemcial phobias in the hopes of convincing customers that since the other guys stuff is synthetic and bad the alts natural stuff must be good. No it isn’t logical but it sure sells snake oil.

  27. Fifi says:

    apteryx – I’m sure that the good doctor will step in if it’s felt that the conversation has veered too far off course, so please don’t use that as an excuse. The sliver of faux respect for the author is just silly in light of your general, generous disrespect for EBM and people who practice it (like, ahem, the author).

    You wrote – “Where botanicals are concerned, one reason people use them is that they are often less potent than drugs – which does not equal worthless – but they are concomitantly a lot safer.”

    Not only did you say that plants are safer than pharmaceutical drugs but you clearly said that the reason people use them is because they believe them to be safer. Then you contradicted yourself by writing –

    ”“There is an assumption sometimes that people who use botanicals believe all plant species are safe for internal use by lay people. This would indeed be ‘ignorant… romantic… odd…’ and reflecting a lack of contact with nature. However, it is what is (properly!) termed a straw man argument. Nobody believes that.”

    Of course you earlier promoted the idea you later denied – which is it? And since you bring up “lay people” perhaps you can tell us how botanicals work differently for lay people than they do professionals? Or are you implying that you’re a trained professional of some kind who offers medical advise and prescribes plant medicines to people? Do you believe that people should use plant medicines under the guidance of someone who’s got expertize in the area so they are using botanicals wisely and appropriately? Or do you believe that they’re safe enough for over the counter use without any oversight?

    No one here is denying that plants have medicinal qualities (as far as I can see) so trying to associate medicinal plants purely with CAM is sheer ignorance – both of the history of pharmacology and the contemporary landscape. Plants can easily be studied using scientific methodologies and are routinely. Certainly pharmaceutical companies, as well as academic medicine and research, put a lot of effort into researching the medicinal qualities of plants and understanding the mechanisms by which they work. They, of course, have to live up to higher standards and test their product for safety unlike the corporations who are selling untested plants as dietary supplements.

    There are a number of reasons that modern pharmacology developed how it did but part of the impetus was to be able to create drugs with a known potency and efficacy so that dosage could be controlled and more effectively administered. With drugs – no matter the form – too much or two little can make a very big difference, a miscalculation can even be fatal. The reality is that even people into “botanicals” rarely actually use the plant in it’s natural form – it’s either dried and then steeped and made into tea, extracted as an oil which is more potent than the original plant, or distilled into an alcohol based tincture.

    Since you’ve been talking about “botanicals” – something you’ve yet to define but clearly a term that refers to plants – I’d have to assume you’re not including Chinese medicine since it often uses animal parts and non-plant ingredients. So what do you mean when you say botanicals? Plants used by European herbalists? Any and all plants used as medicine in any context? (Which would be about as “traditional” as any other new age mishmash.) Do you include homeopathy?

  28. Fifi says:

    apteryx – Do you think licking penicillium mold off bread (or just licking mouldy bread since you’d have to do some science to actually know it was penicillium mould) is safer and more effective than taking penicillin?

  29. Actually Fifi I love old medical books and have a small collection. In one they explain how when the Second World War was looming the Allies knew they would have a lot of injured soldiers with infected wounds and how the US government spent a great deal of money doing the research required to find out how to produce penicillin on a comercial scale. They said that people had been trying to treat themselves and their loved ones with the mold but it wasn’t working. This is from memory. If anyone is interested, I can look for the reference.

    Something similar happened after Banting discovered insulin. A lot of research was required to figure out how to produce a commercially viable product. But my guess is that these are not exceptions but rather the rule.

  30. Fifi says:

    rjstan – If your books have pictures, I am very, very envious! Actually, I’m envious even if they’re not illustrated.

  31. mckenzievmd says:

    Unfortunately, the argument about botanicals vs drugs has distracted from what I found the most interesting and troublesome point of the essay. How do you decide as a clinician what constitutes “better,” and how do you work with a patient who feels they are better as the result of a therapy you know rationally is either unproven and implausible or outright nonsense? We all know anecdotes and personal experience are more compelling that research data and statistics for most people, and we all know that even the best scientists are susceptible to bias and the many sorts of fallacies and thinking errors that also provide most of the supporting “evidence” for CAM. So what should we as skeptics in healthcare do? Is it ok to choose not to try and argue patients out of their erroneous beliefs that CAM has made them better, at least if no obvious harm is being done and they are still amenable to real treatment? Should we even go so far as to recommend treatments like acupuncture and chiropractic, knowing that though they are basically placebos our patients will still feel they are better? Can we deny them comfort even if it is false in the name of truth? Is the risk of encouraging CAM and leading people away from proven scientific medicine great enough to justify trying to discourage people from things that might make them subjectively “better?”

    These are all hard questions I face in practice every day, and don’t have the answers.

  32. Harriet Hall says:

    I think there is an answer. It’s possible to stick to your guns about science without discouraging or alienating patients. If a patient asks about X, be clear that science doesn’t support X but acknowledge that some patients have said they felt better after using it. Say it may be only a placebo effect, but even if it is, what is important is that the patient feels better. Accept the patient’s use of X but work with him to make sure he doesn’t get harmed, scammed, or lost to followup.

    While placebos aren’t ethical, it might be ethical to suggest a treatment if you say up front that it is based on belief but not on science. It’s tricky, because the patient may hear something other than what you’re saying.

    As for arguing patients out of their beliefs, that hardly ever works. It’s better to agree to disagree than to argue. Patients can usually accept that and respect your honesty. As long as you’re disagreeing about the validity of the treatment rather than telling them not to do it.

  33. Actually, I think that the comments do have a bearing on dealing with people who feel better after a treatment which you know can’t be the cause of their feeling better. One of the reasons that such large numbers of people use such treatments and believe that they benefit from them is that they are bombarded with promotional material that comes from press releases passed off as news in papers and on TV as well as from salesmen in stores, on the Internet and even family and friends some of whom are multilevel marketers and they never hear anyone express any doubt as to the claims being made. As a result, when they “try” something they have been told will benefit them and feel better it never occurs to them that it is coincidental or that they have been influenced by suggestion.

    So IMO the more often unsubstantiated claims are challenged, the greater the odds rational people being educated and not deceived. Of course, that does not offer you immediate help with a patient who comes in sure that he has been helped by a placebo.

    I hope some of the doctors discuss this topic with you since it is obviously very relevant. I am not an MD but I do encounter it often not only with silver supplements but with other things I know cannot work the way the person believes they have. I tell them I am glad they feel better but seriously doubt that the supplement or therapy is the reason. I explain briefly why I think that and explain the kind of evidence it will take to convince me that they are correct.

    While I think that the main reason for the problem is that we have failed to educate people in science and even history, I also believe that another component is that psychology has really let us down. They have experiments that illustrate how easy it is to influence people which are actually very entertaining.

    Many years ago Candid Camera had a segment in which they set up a table in a Vermont mall, the home of maple syrup. The had packaged Vermont syrup in containers with palm trees, labled with a name that was something like Sunny Syrup and told people that it was from California. They gave out samples to taste and asked for opinions. Obviously it wasn’t a scientific experiment, but it was educational and funny. The people they showed thought it tasted awful. One insisted that it was molasses. Obviously, they were quite surprised when told that it really was VT maple syrup.

    Another good eye opener for the general public was the comments that followed many of the articles on Airborne. Most were from people certain that the stuff had helped them even after the company settled a lawsuit which was based on the fact that it couldn’t. A few people did admit that they had been conned, and I would guess there were lots more who knew that but never bothered to post comments. It would be interesting to see their before and after sales figures. The point is that for the majority of people reading about the lawsuit and settlement and reading the comments of the true believers would, I believe, make a lot of them realize how easy it is to be wrong about the cause and effect of a drug or therapy. It is just another lesson in how difficult it is to determine the cause of something in a situation with lots of variables.

  34. Fifi says:

    mckenzievmd – “Unfortunately, the argument about botanicals vs drugs has distracted from what I found the most interesting and troublesome point of the essay.”

    I apologize that one thread of the conversation has moved away from what interested you. No doubt both conversations can go on at once :-)

    You just actually illustrated one reason why I thought it important to speak up. In you post you write “botanicals vs drugs” which indicates you don’t think medicinal plants to be drugs. It begs the question, is peyote any less of a drug because it’s in plant form? Are coca leaves not a drug? Is willow bark not used as a drug and where we derived aspirin from? Is St-John’s Wort not a drug? By pretending that “botanicals” aren’t actually drugs (we aren’t discussing homeopathy here but herbalism and plants that have active chemical ingredients that can be studied), not only would we be playing into and propagating the false natural safe/synthetic unsafe meme which CAM is working to spread but any doctor would also potentially be putting their patients at risk if they don’t consider drug interactions.

    As for how to discuss or broach the subject of treatments that have been proven not to work with your patients, wouldn’t that depend on the patient, the situation and how they’re most likely to hear the message? In your experience, how do your patients usually respond to how you try to get your message across?

  35. wertys says:

    As far as the example given in Dr Crislip’s post re acupuncture and neck pain, if the neck pain was due to a myofascial trigger point and it was needled during the acupuncture ‘treatment’ that would potentially explain relief of the neck pain for up to several weeks. Dry needling and trigger point injections are a perfectly valid technique with a scientific rationale and lots of clinical trials to support their place in the diagnosis and treatment of chronic musculoskeletal pain. Some of the commoner acupuncture points are I’m told located over commonly painful trigger points such as the mid-trapezius, rotator cuff and splenius capitis. This may also explain why the technique has developed empirically. It also shows that as scientific knowledge evolves, so should treatments. I haven’t seen any studies of quack treatments for various pain disorders which have tried to limit the treatment under study to one diagnosis, and this especially true for chiropractic and energy medicine studies.

  36. mckenzievmd says:

    Fifi,

    I don’t want to make a big deal out of terminology here. I consider whole ground up plants to be different from isolated and purified compounds produced in standardized forms, the latter I call “drugs.” I wasn’t offering an implicit opinion on the relative pharmacologic effects of the two, but I think they are different in other ways that deserve to be identified by different labels, If you have a different temrinology you prefer, I’m flexible.

    FWIW (which isn’t going to be much), I agree generally with the position already expressed that legitimate scientific study of multiple compunds mixed together in non-standardized amounts is theoretically possible but a lot more problematic than the study of isolated compounds. I understand the argument about the possibility that whole plant extracts might be therapeutically different from individual compounds, but I don’t find it convincing. There is no reason to assume in advance that such extracts would be safer or more effective than isolated compounds (in fact I think there is reason to think they would be less so), and they are certainly harder to evaluate scientifically. I think the history of developing drugs by isolating and studying individual compounds separately has been, while not without problems, much more successful than the trial and error approach to using whole plants as medicine that preceded it. And I’m not convinced there is much to be gained by devoting some of our all too limited research resources into studyng whole plants instead.

  37. Harriet Hall says:

    Wertys said, “if the neck pain was due to a myofascial trigger point and it was needled during the acupuncture ‘treatment’ that would potentially explain relief of the neck pain for up to several weeks.”

    I’m not convinced.

    There is a review article on trigger point injections at http://www.aafp.org/afp/20020215/653.html

    It points out that although trigger point injection and dry needling are widely accepted, there have been relatively few controlled studies.

    It explains the technique used, which doesn’t sound to me like it’s compatible with acupuncture. For one thing, acupuncture uses much smaller diameter needles. For trigger points,”Using a needle with a smaller diameter may cause less discomfort; however, it may provide neither the required mechanical disruption of the trigger point nor adequate sensitivity to the physician when penetrating the overlying skin and subcutaneous tissue. A needle with a smaller gauge may also be deflected away from a very taut muscular band, thus preventing penetration of the trigger point.”

    The article mentions that patients may experience sharp pain, muscle twitching, or an unpleasant sensation as the needle contacts the taut muscular band, which is usually not the case with acupuncture.

    And the response to acupuncture has been shown to have nothing to do with where you put the needles.

    Yes, there is a possibility that acupuncture needles might on rare occasions have a trigger-point effect, but it seems highly unlikely to me.

  38. Fifi says:

    mckenzievmd – I think I understand your reservations about calling plant medicines a drug – you like having a distinction. I think it’s worthwhile making a distinction but if we pretend plant based medicines aren’t drugs not only are we ignoring the history of drugs in medicine (and the fact that a lot of our synthetic drugs originated in nature), not to mention that it propagates the idea that plant based drugs aren’t drugs so are therefore safe. Perhaps making a distinction such as botanical drugs and pharmaceutical drugs would be more palatable to you?

    I’m not advocating one thing or the other regarding conducting trials or trying to study the chemistry but, while it may be simpler for those studying a substance, we already know that in the case of vitamins and minerals that they interact and influence absorption and bioavailablity. I’m not saying that this is necessarily true of drugs but it seems a bit silly to just dismiss the possibility.

    As I noted earlier, there are obvious reasons why it’s actually safer to take a known quantity of a substance of know quality that has been studied (properly, of course) than something as hit and miss as a dried plant (and isn’t regulated, so herbal concoctions are often adulterated, among other potential dangers). Considering the amount of money and effort pharmaceutical companies and researchers put into investigating newly discovered plants or folk remedies that may have medicinal properties, this really isn’t just CAM territory. I see now reason to give it to them when almost all the real work in the area is being done by researchers who aren’t in the least bit woo (though pharmaceutical corporations do tend to have PR departments that certainly weave their own brand of woo – it strikes me as the only people in this discussion who don’t have PR flaks weaving woo for them are doctors).

  39. Mckenzievmd you said, “I understand the argument about the possibility that whole plant extracts might be therapeutically different from individual compounds, but I don’t find it convincing.”

    I think we all understand the argument, but those familiar with the history of drugs including you also understand that just because it is plausible that doesn’t make it true or that if it is demonstrated to be true for some botanicals that it therefore must be true for most of them.

    In my opinion this is one of the primary things that differentiates proponents of scientific medicine from those of the alternative kind. Many alts market products because they have good, plausible arguments that they are safe and effective and in most if not all countries they can get away with that legally. Scientists on the other hand are usually required to present evidence demonstrating that their theories are true. The bar is much higher for them and they don’t get away with demanding that others have to do studies to demonstrate that their beliefs are either true or false, that they have to prove a negative.

    These are things the general public has to understand otherwise they just assume that “the experts have a difference of opinion.”

Comments are closed.