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We get mail

There are a few “laws” of the blogosphere, one of them being that a response to a post that comes more than a few weeks later is generally useless or crazy.  But once in a while, someone takes the time to look at an old post and formulate a thoughtful response.

This is not one of those times.

Or maybe it is.  I’ll report (and editorialize), you decide.

Regarding a piece I first published in September of 2010, a reader writes:

Dear Dr. Gorski:[our managing editor]

I am writing regarding your comments on the following blog

http://www.sciencebasedmedicine.org/index.php/your-disease-your-fault/#more-6747

I am not a doctor but am pursuing an MA and hopefully a PhD in nutrition and public health. I am very familiar with Dr. Fuhrman and his work. I have heard many of Dr. Fuhrman’s lectures and if anything they are all based on concrete scientific research. I must express my disappointment about both the tone and factual content of the article written. I read extensively about nutrition, exercise and their health benefits. Much of the research done in this field has been conducted in small clinical trials or in the laboratory. There is a good reason for this. Only the government has the financial ability to pay the tens of millions of dollars needed to conduct large scale clinical trials in this area since a drug company would in all probability not have any financial gain from a clinical trial showing that individuals eating 10 servings of vegetables each day have a significant reduction in chronic disease. I do feel that all epidemiological as well as clinical work done points to the very clear fact that people die years before they need to due to the poor diets they have. It is also very clear that most physicians have very little knowledge about nutrition since it is generally a very minor part of their education. I agree with doctor Fuhrman that any debate should be both science based and held to the highest ethical standards. From what I see the article written as well as your comments do not meet these standards. I find that most disconcerting due to the fact that individuals put their lives in their hands when they consult with you as a physician.

In closing I would like your comment on the follwing statement that was made by Dr. William Castelli, who ran the Framingham Study for about 20 years. An interviewer asked him what percent of heart disease could be avoided through proper nutrition and exercise. His response was very brief. 100%!! Do you agree with one of foremost reaearcers of the 20th century or do you consider him to be a quack too.

I await your response.

Sincerely,

[Name redacted]

What is instructive here is the usual thoughtful but incorrect “reasoning” used by someone with just enough knowledge to think he understands the topic at hand well enough to rebut.  The rebuttal, however, makes use of the usual fallacies that are the fallback position for the ignorant and the mendacious (and I must point out that I think our Dear Correspondent is the former).

Since I wrote the piece, not Dr. Gorski, I take full responsibility for its content and defend my writing personally.  A bit of a fisking is in order to help us all better understand how to think about these questions properly.

I am not a doctor but am pursuing an MA and hopefully a PhD in nutrition and public health. I am very familiar with Dr. Fuhrman and his work. I have heard many of Dr. Fuhrman’s lectures and if anything they are all based on concrete scientific research. I must express my disappointment about both the tone and factual content of the article written.

The writer first tries to establish himself as an authority on nutrition, public health, and one Dr. Fuhrman (the putative antagonist of my piece) as a reliable source of that authority.  Even if we were to be convinced by his level of authority, it is irrelevant to his arguments.   Our Dear Correspondent could be a Nobel laureate in physics, but this is no guarantee of relevant expertise.

Then he begs the question: he asserts that Dr. Fuhrman’s works are “all based on concrete scientific research”.  This may or may not be true, but it does not refute the points made in my post, such as Furhman’s stated idea that all disease is preventable with just the right lifestyle and avoidance of medication.

He finishes his point with a non sequitur (although one that loyal reader Peter Moran might agree with), that somehow my tone renders my argument less valid.  If I were to point at the sky and shout, “It’s &%$# blue, you ass!” the statement would be no less true for its crudeness.

I read extensively about nutrition, exercise and their health benefits. Much of the research done in this field has been conducted in small clinical trials or in the laboratory. There is a good reason for this. Only the government has the financial ability to pay the tens of millions of dollars needed to conduct large scale clinical trials in this area since a drug company would in all probability not have any financial gain from a clinical trial showing that individuals eating 10 servings of vegetables each day have a significant reduction in chronic disease.

This is simply untrue.  There is an enormous body of research on nutrition and exercise physiology.  Just glancing at today’s issue of the American Journal of Cardiology, we see Impact of Body Mass Index, Physical Activity, and Other Clinical Factors on Cardiorespiratory Fitness (from the Cooper Center Longitudinal Study); from The Lancet, a summary of Salt and cardiovascular disease mortality. These fields (nutrition, exercise) are and have been active areas of high quality research, just not to the exclusion of all else.  It would be rather foolish to focus on only one set of tools to prevent a heart attack.  When lifestyle modification is inadequate, it is not a failure of the patient, the doctor, or science-based medicine, but a simple case of “stuff happens” and it’s time to crack open another tool box.

These facts render irrelevant his subsequent suspicion-filled assumptions about the economics of medicine.  The government funds a great deal of this research, but so do pharmaceutical and related industries.  There is always a profit to be made, whether by developing a new drug, or opening a Whole Foods with aisles full of magic (some of which is quite healthy and quite tasty).

I do feel that all epidemiological as well as clinical work done points to the very clear fact that people die years before they need to due to the poor diets they have. It is also very clear that most physicians have very little knowledge about nutrition since it is generally a very minor part of their education.

Not to wax Crislipian, but Duh! Our country is suffering from an epidemic of obesity, leading to early, preventable deaths.  That’s not particularly controversial.  It’s also not a mystery that many physicians receive an inadequate education in nutrition.  The fallacy here is that it is better to worship a false god than to seek true knowledge.  The cure to our ignorance is not to listen to some pseudo-expert who is completely wrong about disease prevention and treatment, but to improve our education of the public and our professionals.

I agree with doctor Fuhrman that any debate should be both science based and held to the highest ethical standards. From what I see the article written as well as your comments do not meet these standards. I find that most disconcerting due to the fact that individuals put their lives in their hands when they consult with you as a physician.

Well, that’s just ad hominem nonsense.  What counts is facts, not one writer’s opinion about tone and ethics.  This statement betrays a complete misunderstanding of medical ethics.  Our duty, as physicians, is first to our patients, then to the wider public.  We must treat the patient in front of us with the best science-based medicine has to offer, delivered with compassion.  We must educate the public to teach the difference between real doctors and carnival barkers (h/t POTUS).

In closing I would like your comment on the follwing statement that was made by Dr. William Castelli, who ran the Framingham Study for about 20 years. An interviewer asked him what percent of heart disease could be avoided through proper nutrition and exercise. His response was very brief. 100%!! Do you agree with one of foremost reaearcers of the 20th century or do you consider him to be a quack too.

I’m not so sure about that Castelli quote.  He has a history of some pretty bold pronouncements that don’t quite follow the evidence, but if you dig into his efforts a bit deeper, you can see that he clearly doesn’t believe the statement above:

Castelli concedes diet and exercise won’t help the 5 to 10 percent of people who’s heart disease is genetic. The genetic predisposition to heart disease is responsible for 85% of heart attacks suffered by people under 65. These people often have cholesterol levels of a whopping 300 or higher. Medication can save their lives, but the health care system, Castelli charges, doesn’t do a good enough job of finding these patients in time.

If our Dear Correspondent would like to learn more about how to think more clearly about medicine and science, this blog has been live for a few years now and offers a treasure trove for those interested in banishing ignorance, or at least learning to tell fact from its opposite.

Posted in: Science and Medicine

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97 thoughts on “We get mail

  1. Jojo says:

    I do a great deal of reading on the research into nutrition and exercise as well. While it does seem clear that good nutrition and regular exercise play an important roll in good health, I’ve never read anything that shows that it’s the only thing that’s necessary. In fact, from what I’ve been reading, there is a good bit of evidence that complex factors such as hormones, exposure to light, societal driven sleep patterns and such may all play a roll in making it virtually impossible for many people to maintain a healthy BMI and meet even the basic dietary and exercise guidelines set by the government.

    So, even if it were possible to prevent all disease through nutrition and exercise, the science seems to show that for some people it is impossible for them make the very changes that your letter writer is claiming are such a panacea.

    The letter writer complains of tone in your post, but seems to miss the blatant arrogance of insisting that people simply need to eat right and exercise, which is no different than calling people with poor health undisciplined and lazy.

  2. windriven says:

    It appears to me that the central argument of this correspondent lives here:

    “I do feel that all epidemiological as well as clinical work done points to the very clear fact that people die years before they need to due to the poor diets they have.”

    Translation: Poor diet and lack of exercise are the one true cause of disease.

    “I do feel…” Who cares? What does the evidence say?

    “that all the epidemiological” Citations?

    “as well as clinical work done” Citations?

    “points to the very clear fact that people” Which people? Americans? Chinese? Azerbaijanis? All have very different diets and levels of physical activity.

    “die years before they need to” Years? How many? Based on what frame of reference?

    “due to the poor diets they have.” As Dr. Lipson noted, most everyone agrees that obesity and physical indolence have demonstrable negative health consequences. But presuming that these are outliers and that the baseline is an individual of nominal BMI, exactly what diet is required to achieve these additional years of life?

    If the idea is that one can live forever by eating nothing but alfalfa sprouts and brown rice I’d like to point out that you still won’t live forever. But with a diet like that it will seem like forever. ;-)

  3. Peter Lipson says:

    If the idea is that one can live forever by eating nothing but alfalfa sprouts and brown rice I’d like to point out that you still won’t live forever.

    Not to mention it’s always the sprouts.

  4. maeris says:

    Dr. Lipson, I hope you don’t mind if I forward this article onto people the next time I have an argument about this! I work in a lab that does clinical studies on nutritional interventions for cardiovascular disease, and so I’m acutely aware of what’s out there. One of our favourite references in proposals and the like to use is the INTERHEART study (Yusef et al., Lancet, 2004), which found that up to 90% of cardiovascular disease could be accounted for by modifiable risk factors. This is in opposition to non-modifiable risk factors, like age, genetics, gender, etc. (As a side note, Dr. Salim Yusef is a brilliant speaker and I highly recommend attending his talks if you ever have the opportunity.) Non-modifiable is quite different than “can be treated with only diet and exercise” – one of the major factors Yusef et al. identified was smoking! Hyperlipidemia, hypertension and diabetes were also major effectors, and yet so many people fail to apply common sense. If diet, exercise, and other lifestyle interventions fail, the next step to modify the modifiable is with drugs! Indeed, Dr. Yusef’s work beyond INTERHEART has been the creation of a “Polypill” containing 100 milligrams of aspirin, with simvastatin (20 mg) and low doses of three blood pressure medications, atenolol (50 mg), ramipril (5 mg) and thiazide (12.5 mg).

    Does Dear Correspondent mean to say that we should abandon those diabetics who already do exercise and eat well (or perhaps those who cannot exercise) to their own devices and deny them appropriate pharmaceutical interventions? Do they think that those hypertensives who are already on a low-sodium diet are just whining about it?

    Nutrition and exercise may be important potential low-risk, low-cost interventions, but that hardly necessitates throwing other science-based treatments out the window. Non-complicance can happen for many reasons other than laziness, and a gross over-simplification of this issue does little more than condemn those who are ill. It seems hardly fair to accuse SBM of having a lack of ethical standards when DC’s seem to be “run harder, fatty!”

  5. I always wonder, isn’t living longer a rather an arbitrary goal?

    Sure, many folks want to live a long time, they want to live life in a healthy, functional state. The also want to enjoy their life, their meals, etc…who want to to live a life perpetually sacrificing to reach an end point (reaching 100 of age?) that is not inherently rewarding. If you die at 80 are you really going to miss those last 20 years?

    Sometimes I think it’s just competitiveness. As if someone’s going to give you a medal at the finish line.

  6. Scott says:

    Typically the woomeisters claim that there is no tradeoff. Not only will their magic diet make you live forever, it’s also the tastiest and easiest to prepare food ever! And it’ll make you the greatest genius in history! And prevent global warming! And eliminate dependence on foreign oil! And ensure 0% unemployment and 20% annual GDP growth!

  7. GLaDOS says:

    Off topic, but this is breaking lulz: Mike Adams the Health Ranger in old Scientology promotional video. It’s a kind of “We are the World” thing that will give you 1980s flashbacks.

  8. WilliamLawrenceUtridge says:

    Dr. Barrett over at Quackwatch made a cogent point in the past – doctors don’t take a “nutrition” course. They take multiple courses in anatomy, physiology and organ/disease function/disfunction where the enzymatic pathways and metabolic flows of nutrients including vitamins are explored in detail. There’s no one course focusing on diet and nutrition, instead it is stitched through the entire curriculum and a very fundamental, biochemical level. Doctors don’t necessarily get training on what menus to prepare, but they know what you need to eat, and what tests to take to verify you are getting enough or not. And since there is no magic beans or miraculous fruit (sorry acai berry) that guarantees life, health or longevity, there’s no effin’ reason to do much more than recommend exercise and eating fresh fruits and vegetables, a small amount of meat, cheese, milk, nuts and other protein/fat-rich foods, and try to keep the mayo and candy to a minimum. Really, you can’t go wrong with the most basic and fundamental advice – eat a variety of fresh foods you prepare yourself. Diet won’t make you live forever, but it will help if you actually follow the advice we’ve been hearing for years. Food’s not magic. It’s just food.

    http://www.quackwatch.com/04ConsumerEducation/nutritionist.html

  9. GLaDOS says:

    How many courses on electrons do physicist take for their degrees? None! That’s why you should see an electronologist instead of a physicist for really vital electron issues.

  10. David Gorski says:

    He finishes his point with a non sequitur (although one that loyal reader Peter Moran might agree with), that somehow my tone renders my argument less valid. If I were to point at the sky and shout, “It’s &%$# blue, you ass!” the statement would be no less true for its crudeness.

    Heh. I’ll have to remember that one and steal it sometime. :-)

  11. pedsnurse says:

    Michael Pollan in his book “Food Rules” said it best “Eat food, not too much, mostly plants”

  12. wales says:

    In defense of exceedingly tardy reader comments on SBM blog posts: I have been guilty of this myself and I defend the practice for two reasons. SBM’ers should be pleased that their readers are doing some deeper delving into past posts rather than merely skimming the daily offerings, especially for readers new to the site. Also, as new discoveries are revealed in the field of medicine it is often worthwhile to revisit the past posts to update the topic. In fact, if the authors of this site are serious about its longevity and accuracy they might consider addendums to their posts when warranted.

    For example, I was recently tempted (but didn’t have the time) to comment on a SBM post that I read on the subject of magnets and health (perhaps a year ago?). As I recall, that post commented to the effect that because the iron in blood is not ferromagnetic, magnets couldn’t possibly have any effect on blood or health. This was only half-true: because the iron in blood is paramagnetic red blood cells can and do react to some forms of magnetism. This may be beneficial by reducing blood viscosity.

    http://www.sciencedaily.com/releases/2011/06/110607121523.htm

  13. Scott says:

    Ah, but paramagnetic effects are so much weaker he had to use a huge whopping magnetic field to get an effect. I believe you’re referring to:

    http://www.sciencebasedmedicine.org/index.php/can-magnets-heal/

    Which discusses fields orders of magnitude weaker. In other words, the objection is immaterial.

    For another reason, too – the ferromagnetism comment was specifically in the context of claims that the iron was somehow special. Which is only the case in contexts where it IS ferromagnetic. Paramagnetism is exceedingly common, and iron’s nothing special there.

  14. Zetetic says:

    Dr Fuhrman’s technicolor web site is a real hoot! Of course, there’s a “Shop” tab.

  15. wales says:

    “the objection is immaterial”…actually, I wasn’t “objecting”, I was pointing out the importance of qualifiers in parsing detailed information, as well as the importance of new information.

    You may find it immaterial, but those “huge whopping” magnetic fields are used (and overused) in medicine on a daily basis, so perhaps this will become a valid treatment for some at a future date.

  16. Scott says:

    Since any given individual only gets exposed to such fields on very rare occasions, the fact that somebody is getting an MRI each day doesn’t keep it from being immaterial. There is absolutely no chance that anyone will ever be exposed to a field within orders of magnitude of that strength for any significant fraction of their life.

    It’s an interesting curiosity, certainly. But there isn’t any indication whatsoever that there is any potential at all for a useful treatment.

  17. JPZ says:

    @WilliamLawrenceUteridge

    That’s great that you take courses in anatomy, physiology, etc. Those courses do contain pieces of nutrition information, but they are taken out of their nutritional context. There is a need for that context or you can have embarrasing discussions like the OB/GYN who told me that lactation causes iron deficiency or the internist who only mentioned broccoli as a potential problem for warfarin treatment. I only mention these examples because they illustrate a lack of nutrition system biology knowledge, not because I consider these misconceptions typical (a couple of weeks ago, I had a urologist blow me away with his detailed knowledge of nutritional biochemistry).

    The problem of inadequate nutrition training in US medical schools (there are schools that are exceptional exceptions) is not new and is being addressed (http://www.aafp.org/online/en/home/publications/news/news-now/resident-student-focus/20101020nutritioneduc.html). I only mention this UNC program because I know people involved in it.

  18. Angora Rabbit says:

    @JPZ
    Thanks for the link. I was going to mention the same program. I agree with you that there is a lack of coherent nutritional training in many med schools. The UNC program is an outstanding attempt to address the gap. It continues to be a frustration because nutrition is seldom a required topic in many med schools (at my med school it is an optional 2nd yr course). And while WLU is right that it is touched on in diverse courses, it’s not the same as pulling it all together into a comprehensive, dedicated course. Too many trees, not enough forest.

    To change the subject, our nutrition grad program receives 2-3 applications each year from people like Dr. Lipson’s letter writer. They are convinced that nutrition is the be-all-and-end-all to all diseases and thus want to study it. Alas for them, their statements invariably betray a devastating absence of critical thinking. Since it costs my research grant $34K annually to train a grad student (excluding lab costs), these folks will not receive an acceptance letter. Your letter writer may be similarly doomed unless he develops critical thinking skills and stops being wedded to his hypothesis. Instead he will claim it is a “conspiracy” to silence his original thinking, when instead it reflects the applicant’s lack of original thinking.

    @Geoff’s link on ADK last week sent one to a blog writer with exactly the same deficit, which is why these two posts triggered this train of thought.

  19. Anthro says:

    When I was diagnosed with Type II diabetes, I was told to lose weight and sent promptly to a Registered Dietician who told me what I already knew–only spelled it all out and gave me lots of materials and ideas to help make it happen. I lost the 50 lbs, have kept it off for five years now and have normal blood sugar, much lower blood pressure (much lower doses of meds), almost normal triglycerides (take a small dose of statin to keep numbers extra low because of family history), and even raised my HDL into the normal range for the first time! I don’t exercise beyond brisk walking and gardening. I no longer take metformin as my blood sugar has remained normal since the weight loss.

    I didn’t really change anything as I’ve always eaten as M. Pollan suggests–it’s the “not too much” part I had to wrestle with.

    My point is, that a Registered Dietician is an expert in nutrition who works in conjunction with your physician, so what’s the big deal whether or not doctors have the ideal (whatever that is!) amount of nutrition education? I think Dr. Barrett’s point about basic science training is very well taken.

    Even if all doctors were nutritional gods, would that make most people follow their advice? I am told that what I have done is only accomplished by about ten percent of those who attempt it–and there are many who don’t even try.

    And what about genetics? The old lady (90) two doors down has never eaten anything but supermarket food and mostly meat with very few vegetables. She walks and gardens and is in great shape. She also recently had a quadruple stent surgery and is very happy now that her chest doesn’t hurt anymore–but she made it to 89 before needing this!

    I have a number of family members who have been told over and over to lose weight or they are going to die (especially the ones that don’t take their meds either) by their doctors. How does the number of hours the physician spent on nutrition help these people? Perhaps more hours of phychology or a referral to a psychiatrist would be more helpful than nutrition courses. Can anyone really think that doctors should spend their time making menu plans? They already know the chemistry behind the nutrients required for “health”, the rest is a matter of balance and portion control–that’s what the dietician does, and none of it will help unless the patient is motivated.

  20. wales says:

    Scott said “there isn’t any indication whatsoever that there is any potential at all for a useful treatment.” Uh, you might want to read more carefully next time.

    There was no expectation or implication that individual’s need to be continuously subjected to the necessary “huge whopping” magnetic fields in order to benefit.

    “When the magnetic field was taken away, the blood’s original viscosity state slowly returned, but over a period of several hours. Tao said that the magnetic field method is not only safer (than aspirin), it is repeatable. The magnetic fields may be reapplied and the viscosity reduced again. He also added that the viscosity reduction does not affect the red blood cells’ normal function.

    Tao said that further studies are needed and that he hopes to ultimately develop this technology into an acceptable therapy to prevent heart disease.”

  21. Harriet Hall says:

    @wales,
    The article says it reduces blood viscosity by linking red blood cells together in short chains. I’m having trouble envisioning how this would improve blood flow, as it would seem to make the blood lumpy and more likely to clog up or stick on arterial plaque. I can’t help but wonder if that might have some adverse effect.

  22. wales says:

    HH, thanks for input. Anything is possible and there is always the potential problem of unintended consequences, but the results seem promising at this early stage. Although the resulting chains are larger than single blood cells (hence your “lumping” comment, I presume), because the viscosity is reduced the blood flow is streamlined and friction is reduced…..

    “…the magnetic field polarizes the red blood cells causing them to link together in short chains, streamlining the movement of the blood. Because these chains are larger than the single blood cells, they flow down the center, reducing the friction against the walls of the blood vessels. The combined effects reduce the viscosity of the blood, helping it to flow more freely.”

  23. Josie says:

    @Glados

    Actually I have taken a course on (pushing) electrons –it was called Organic Chemistry :P

    I’m thinking we should seek the services of a chemistry professional for all those vital electron needs

    /tongue now out of cheek :)

  24. JPZ says:

    @Anthro

    I never suggested that physicians provide the same services as dieticians, so please stick to the point. The National Academy of Sciences (ref. previous post link) recommended 25 hours of nutrition instruction for medical students, i.e. that is the answer to your “whatever that is.” I’ve addressed why I believe the disconnected facts that medical students presently learn about nutrition do not address nutrition in a systems biology context, and why I believe the lack of this context affects accurate diagnosis and quality of patient care. As I said, the belief that nutrition education in US medical schools is inadequate is not new and not solely my own (http://journals.lww.com/academicmedicine/Fulltext/2010/09000/Nutrition_Education_in_U_S__Medical_Schools_.30.aspx ; esp. see Ref 1-4). Again, steps are being taken to address this concern and progress is being made.

    And P.S., please try not to summarize the field of dietetics as “menu planning.” You might P.S. (piss some) dieticians off. They are broadly trained health professionals.

  25. daedalus2u says:

    What about Reggie Lewis, he died of a heart attack at age 27, during his prime.

    http://en.wikipedia.org/wiki/Reggie_Lewis

    What diet or exercise changes could he have made to prevent a heart attack?

    I am very skeptical of this report on magnets and blood flow. I think it is bogus.

    It is only deoxygenated hemoglobin and methemoglobin that is paramagnetic. Oxyhemoglobin is diamagnetic. The particle chaining effect would only occur in venous blood. Virtually always restrictions in blood flow occur on the oxygenated side. It is on the upstream of capillary beds that the control of flow through that bed is mediated. Under reducing conditions, deoxyhemoglobin becomes a nitrite reductase and generates NO, which dilates blood vessels and would open up any downstream vessels that were constricted.

    In capillaries blood cells go through single file. It is quite implausible that clumps of blood cells could remain in the blood stream long term. Aren’t clumps like this called clots? Chaining of particles is well known in dielectrophoresis and in magnetic separation. Only ferromagnetic particles that become permanent magnets continue to chain after the magnetic field has been removed. Blood cells are not ferromagnetic, oxygenated blood cells are not even paramagnetic.

    A very strong magnetic field would tend to cause anti-chaining of diamagnetic particles.

    Rongjia Tao has a number of patent applications on treating things with magnets with dramatic claims but without a plausible physics based explanation. This is simply another in a list.

    I suspect it is an artifact of how they are measuring blood viscosity.

  26. pmoran says:

    He finishes his point with a non sequitur (although one that loyal reader Peter Moran might agree with), that somehow my tone renders my argument less valid.

    Thanks for the mention, Mark. I am sure you know that I have rarely, if ever, personally used the word “tone”, but that I support the view that some approaches can be a barrier to fruitful communication. They can be frequently observed terminating it. They may also erroneously suggest that the author holds extremist views.

    An example I have previously offered: CAM supporters may well deduce from the “tone” of some of the discourse here that the authors would, if they could, ban alternative medicine altogether, so that conventional medicine was the only option.

    They are inclined to believe this anyway, and find it incomprehensible that anyone would want to do this other than to protect someone’s profits. So why would we risk reinforcing such perceptions?

    When challenged, no one here ever admits to having such an objective, but especially with there never having being any clear explanation of the objectives of this group regarding “alternative” medicine, readers are free to make their own deductions.

    A more recent example is the reaction to the Atlantic discussion.

    I haven’t read it all and I am sure that much of it would be objectionable to me too, containing the usual distortions of the facts that CAM practitioners try to justify themselves with. Yet all the frothing at the mouth at this piece could have been moderated by a some realizations that do accord with reality.

    1. These authors are neither ratbags nor frauds. Motives will surely be mixed, as always, but at heart they probably have the same aims as us — achieving the best possible outcomes for their patients and for the general public. They are also not making many outrageous of frankly dangerous medical claims

    2. Freedman is explicit in accepting that homeopathy, and by implication other CAM modalities, “work” because “they rely on the placebo effect and the practitioner-patient interaction, not on the details of the treatment.” . That is also common ground.

    Andrew Weil is essentially conceding the same when the presumed very best examples for the supposed “scientific” efficacy of CAM that he can come up with are saw palmetto and red yeast, two herbals that contain pharmacological active ingredients (adulterant estrogens in at least some samples of the former).

    This adds to evidence that the less batty elements of CAM are close to conceding that their characteristic theories are little more than a necessary “schtick” on which to structure other helpful interventions. They simply cannot ever say so because of all the mud sticking to that P word. Are they talking in a code that perhaps the so-called “shruggies” and “accommodationists” can read, but those here cannot?

    (The preventive medicine aspect, BTW, is not in the least helpful to CAM — preventive medicine should be taught in schools and on TV — not through having to pay someone for it)

    3. This element of CAM isn’t setting out to corrupt medicine, destroy science or defraud the public, as the explicit content, if not the “tone” (whatever that is) of much skeptical discourse suggests.

    There is not the slightest basis for believing that they have not had such strong experiences within their practices that they are convinced that that their overall patient management does work, and often seems to when the mainstream has not.

    And some of the science does back them up –

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001416/?tool=pmcentrez

    I have always personally had some sympathy for practitioners who get sucked in by the various powerful illusions that operate within medical practice. It truly is a (metaphorical) “there, but for the grace of God, go I” situation.

    Adding to all the well-known illusions, evidence such as the above suggests that in many clinical settings “irrational” CAM methods can perform as well as our pharmaceuticals! The evidence is not yet conclusive as to the full strength of “non-specific effects” because the studies cannot be blinded, but we may well get some surprises as further pragmatic studies are performed.

    So one of my concerns is skeptics locking themselves into positions concerning the practical medical aspects of CAM that may become increasingly difficult to defend as further evidence rolls in.

  27. nybgrus says:

    And yet none of that can get past the “placebo is unethical” point, regardless of how great the magnitude of non-specific effects may be.

    Show me a case where placebo has a significant, sustained, and objective benefit and I will pause for a second and think. And then still conclude that placebo is unethical to give as a treatment. But I reckon you can’t even show me such a case to begin with.

  28. WilliamLawrenceUtridge says:

    Meh, my overall point was that doctors do get training and education in nutrition, though at a biochemical level rather than a physiological level. When CAM nutters say “doctors don’t get any training in nutrition” it means two things:
    #. They’re wrong, and they’ve not been to med school
    #. They really mean “doctors don’t get training my particular ‘one cure to all diseases’ brand of nuttery”
    Doctors know enough about nutrition to counsel the average person – eat less, eat better. They also have knowledge of nutrition-based disease states like phenylketonuria. I can’t find myself upset with a doctor who recommends Canada’s Food Guide or whatever the US equivalent is because that will be good for most people. If you’ve got a dietary difficulty like celiac disease (and real disease, not “it causes all the ills of civilization but doesn’t result in diarrhoea or any other hallmark symptoms”) chances are they’ll refer to a specialist. But no matter what, there’s no magic bullet, no one food or pattern of food consumption that prevents and cures all disease and lets you live forever. That’s what med school teaches you.

    Or so Stephen Barrett tells me :)

  29. wales says:

    Daedalus, I haven’t read Professor Tao’s paper, perhaps you have? In any case, it appears that your conclusion is that the physicist is in the habit of publishing papers on theories which lack physics-based explanation?

    I did see that Tao is affiliated with several patent applications, many of which have been assigned to Temple University.

  30. JPZ says:

    @WLU

    You might want to get that Dunning-Kruger effect checked out by a nutrition scientist. You don’t want it to turn into something serious. :)

    (I had a long post written up with links and statements from the American Association of Medical Colleges, American Medical Student Association, National Institutes of Health, etc. plus surveys of physicians stating lack of nutritional counseling knowledge – it was just chock full of information. Then, I went to my Favorites to get one last reference, and lost the whole thing. When will I learn to use MS Word rather than writing on the fly!)

  31. Zetetic says:

    I wonder if they are using the very woo-full “Live Field Microscopy” to identify RBCs that are in chains. The very unscientific analysis of blood by this dubious methodology produces many artifact effects like rouloux which those who practice this quackery interpret in fantastical ways.

  32. “Show me a case where placebo has a significant, sustained, and objective benefit and I will pause for a second and think. And then still conclude that placebo is unethical to give as a treatment. But I reckon you can’t even show me such a case to begin with.”

    I couldn’t follow this line of argument, but here is my example: psychotherapy.

    However, we caqll them, “nonspecific therapeutic factors,” rather than “placebo effects.” Read Carl Roger’s views and Irvin Yalom’s views of how people in emotional distress, and deperssion, get better through psychotherapy.

    “Instillation of hope,” “unconditional positive regard,” and so on. This is how the enrollees in antidepressant trials get better: they get placebo efefcts, plus the convincing nocebo effect of side effects. These effects are sustained for some. Some need those effects, plus the actual influence from interpersonal process (stack sullivan), CBT (ellis, beck), or other “specific” psychotherapeutic factors.

  33. Harriet Hall says:

    MedsVsTherapy,

    I’ve heard the argument that side effects from antidepressants distort trial results because they reveal to blinded subjects that they are getting the real thing. It makes sense, but is there any hard evidence to support that interpretation? Were “exit polls” done asking if patients could guess whether they were in the drug group or the placebo group? If they can guess better than chance, blinding has been broken and it’s not a good study.

  34. pmoran says:

    Nybgrus: And yet none of that can get past the “placebo is unethical” point, regardless of how great the magnitude of non-specific effects may be.

    The ethical concerns don’t click in until there is the strong conviction that it IS “only” placebo. So they apply to, — well, only us, our tiny, but supposedly enlightened scrap of humanity, leaving the rest free to do what they will. And not all doctors see it the same way, either.

    We somehow find ourselves at a bizarre end of normal human cautiousness. We would prefer to forgo potential benefits, even for ourselves, rather than risk being misled by placebo effects.

    No one else has that worry and it is not clear to me how far we should go to impose it upon everyone else, when so often it just does not matter that some nonsense or other has been of help to them.

    Show me a case where placebo has a significant, sustained, and objective benefit and I will pause for a second and think. And then still conclude that placebo is unethical to give as a treatment. But I reckon you can’t even show me such a case to begin with.

    I am an unrepentant mind-body dualist, in one sense. It is absurd not to see some human responses as effects of “the mind”, even though it is all based upon physical processes.

    So I prefer to believe, too, that placebos don’t usually have objective effects upon disease processes, despite some oddities such as preliminary studies suggesting effects upon cardiac outcomes.

    I suspect that placebo responses can wear off, too, although, again, some studies do show enduring effects from sham acupuncture, and we don’t have information on what happens if such “treatment” programs are then repeated.

    The clinical significance of non-specific effects including the placebo is the whole issue. I simply don’t think we can have a rational attitude towards the old style medicine of CAM, the kind that has served mankind for millions of years, until last Wednesday, unless we have a clear answer to that.

    At present the evidence is weighing in favor of a strong possibility of clinically useful effects. That possibility suggests a more cautious approach than is usual within skeptical circles, until more evidence is in.

  35. nybgrus says:

    @meds:

    I admit that I am not particularly well informed on the topics of psychotherapy, but I would argue that your examples do not violate my claim.

    First off, any change in mentation (such as depression) is by definition a subjective one. Sure, there are objective endpoints such as suicide, but in general you can’t hook someone up to an EEG and quantify their level of depression.

    Secondly, I would consider psychotherapy to not be a placebo since you are giving something active in kind for the pathology present. In organic disease we treat the basis of that disease on a molecular level (or macroscopic surgical level). In mental pathology we use things like CBT and/or pharmaceuticals to alter brain biochemistry. I don’t think that psychotherapy alone can be considered a placebo since it is demonstrated that events and discussions can actually physically change the neural organization and biochemistry of the brain. It is obviously very difficult to do any quantify, but I would argue that a psychotherapist who succesfully treats a patient’s depression will have effected a specific effect on the brain chemistry – not a placebo. That may change and relapse, but so may hypertension when meds are removed. That doesn’t make it any less of an active and (potentially) objective intervention.

    @pmoran:

    The ethical concerns don’t click in until there is the strong conviction that it IS “only” placebo. So they apply to, — well, only us, our tiny, but supposedly enlightened scrap of humanity, leaving the rest free to do what they will. And not all doctors see it the same way, either.

    So essentially you are saying it is ok to shuffle them off to and endorse (tacitly or not) others who don’t have a sense of their craft being placebo in order to achieve a clinical end goal? I find that untenable. If you suspect it is likely to be only (or even predominantly) placebo then your ethical concern must kick in. Because, as has been demonstrated here innumerable times, this is not a case of only benefits with no risks. So even if it isn’t only placebo and there is some small other effect, it doesn’t matter. The benefits don’t outweigh the risks. And as professionals who have chosen to undertake extra study, training, and expertise and sworn to an ethos of service, we have extra duty and responsibility to ensure those standards be held.

    No one else has that worry and it is not clear to me how far we should go to impose it upon everyone else, when so often it just does not matter that some nonsense or other has been of help to them.

    And this is where you and I fundamentally differ and you use language to frame your argument so as to make the likes of me sound downright nasty as a result. It is the old “are you still beating your wife” question.

    We do not strive to “impose” it on others. We strive to enforce a single standard for all that would propose to practice anything with a health claim. In terms of the population at large, we do not strive to “impose” our mentality on them, but instead educate them so they may be more able to make a more informed and accurate decision.

    You continually frame your claims in the sense that we are wishing we could run around willy nilly, slapping the needles out of acupuncturists hands and calling their clients raving idiots. Nothing could be further from the truth.

  36. daedalus2u says:

    First, I consider psychotherapy to be a placebo because it has real physiological effects not mediated through pharmacology, surgery, or other physical mechanisms but via communication.

    Transmyocardial revascularization is the attempt to revascularize the heart from the inside by using a laser to blast channels through the heart muscle from the inside with the idea that these channels would be sites from where vascularization could occur.

    Initial unblinded trials were pretty successful, blinded trials were not.

    http://www.ncbi.nlm.nih.gov/pubmed/12929105

    http://www.ncbi.nlm.nih.gov/pubmed/15596031

    However, some of the placebo subjects in the blinded trials did experience what was considered to be “real” improvement that was greater than that of “standard treatment”. Transmyocardial revascularization may or may not be a placebo (I think it is). However the placebo treatments that were used to blind the patients were placebos, and they did seem to have positive effects.

    But if you want to quibble about which placebos can have real physiological effects (the correct answer is all of them), then you have to settle on an unambiguous definition, and the definition can’t be “treatments without physiological effects” because then you have defined “placebo” such that they can have no physiological effects and so any positive effects that you see are (by definition) due to non-placebos.

    Placebos are still unethical when they are misrepresented to be something different than what they are. Psychotherapy is not misrepresented to be something different than what it is. Using laser transmyocardial revascularization as a placebo is unethical.

  37. JPZ says:

    @Harriett

    I have rarely used the exit interview to query a break in the blind, but I did have a break in a vitamin C study. Subjects could apparently bite the tablet in half and taste whether vitamin C was present (no visual clues though) – we put citric acid in the placebos thereafter. I would hypothesize that a treatment effect large enough to break a blind would trigger a data safety monitoring board to end the trial (unethical to proceed with placebo treatment due to unexpectedly high efficacy).

    @MedvsTherapy

    The clincher for me in psychotherapy studies have been the meds + therapy vs. meds alone trials – lots of support for the benefits. Wouldn’t good placebos for CBT be freudian analysis, religious advisors, or meditation? In my field, weight loss studies will often compare dietary counseling to handing people brochures where the same information can be conveyed but not with professional insight and interpretation.

  38. daedalus2u says:

    I have not read professor Tao’s paper. I have read his patent application and glanced at some of his other work (and was not impressed). In my day job before I became a nitric oxide maven (and which I am still active in), I worked (~20+ years) in field mediated separation, especially electrostatic but also magnetic and dielectrophoretic. The “chaining” of particles is seen in all of these techniques and results from the field being focused by the particles. For the particles to “chain”, they have to experience a net attractive force and for that to happen the particles have to have a dielectric constant or magnetic susceptibility higher than the fluid they are in. Oxygenated red blood cells do not have a magnetic susceptibility higher than the fluid they are in, so they cannot “chain” due to magnetic effect. The force actually causes anti-chaining.

    If deoxygenated red blood cells did chain, they would de-chain as soon as they became oxygenated.

    Maybe he is seeing a real effect of high static magnetic field on blood viscosity or blood pressure. If so, that effect is not due to red blood cell chaining.

    Diamagnetic and dielectrophoretic effects go as the field squared. 1.3 Tesla is a high field. There have been MRI studies in humans at 3 Tesla and even 7 Tesla. Here is a study in mice at 17.6 Tesla.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069968/?tool=pubmed

    If there was noticeable chaining at 1.3 Tesla, there would be 180 times more at 17.6 Tesla. If there was “chaining” at 1.3 Tesla, (which the magnetic properties of blood very strongly argue against), there could well be blockages at 17.6 Tesla.

  39. daedalus2u says:

    JPZ, If you want to look at the effects of placebos, you have to define what you mean by “placebo”. To me, CBT, Freudian psychoanalysis, religious counseling, all types of psychotherapy by any technique are all placebos because they all have “real” effects which are not mediated through drugs, surgery, or other physical treatments.

  40. JPZ says:

    @daedalus2u

    I see your point, but I would allow the definition of “active” to include interventions of any nature intended to provide the hypothesized outcome, e.g. traffic light cameras vs. police patrols. It is just a different point of view.

  41. Angora Rabbit says:

    @WLU – since nutrition is a field that combines physiology and biochem, getting only half the training isn’t adequate training, which is exactly JPZ’s point. I train dietitians (and can we spell this correctly please?) and the ADA requires coursework in (among other topics) chemistry, organic chem, biochem, physiology, zoology, and psychology, in addition to multiple classes in nutrition and food science. Dietetics is about a lot more than dietary counseling. They need to be able to handle a range of conditions from HIV to cancer, renal failure to CVD, head trauma to pregnancy. And be pretty fair psychologists like most health care professionals, as they have to try and change ingrained behavior.

    “But no matter what, there’s no magic bullet, no one food or pattern of food consumption that prevents and cures all disease and lets you live forever. That’s what med school teaches you. ”

    That’s what my nutrition colleagues have been teaching for decades too, and there we can agree. :)

  42. daedalus2u says:

    JPV, then by your definition, acupuncture can’t be a placebo because it is intended to be an active treatment. Reiki can’t be a placebo because it is intended to be an active treatment. Neither can prayer, or even distance healing.

    Even sugar pills that are given with the intent of tricking the patient into feeling better cannot be placebos by your definition.

    If you want to discuss the physiology of the placebo effect, you can’t define it away by overspecifying your definition of the effect you are trying to measure.

  43. David Gorski says:

    Yet all the frothing at the mouth at this piece could have been moderated by a some realizations that do accord with reality.

    Interesting. Characterizing how some of us, such as Steve Salzberg, Steve Novella, and myself, have complained about The Atlantic article as “frothing at the mouth” is exactly the same sort of “tone” and language you regularly castigate some of us for. You appear to be quite willing to use insulting language and a harsh tone when it suits your purpose; so please explain: Why is it OK for you to use such language and tone to criticize your (mostly) allies but when we do it it’s so very, very counterproductive? This is not an isolated example, either. I recall seeing you do this on several occasions over the last three years.

  44. nybgrus says:

    @daedalus: I can see your point, but I disagree with your definition.

    From an article on the topic in the Annals of Internal Medicine:

    “The one thing of which we can be absolutely certain is that placebos do not cause placebo effects. Placebos are inert and don’t cause anything.”

    So in psycotherapy, if your verbal discourse with the patient produces an actual change in their brain chemistry/architecture then it is not a placebo treatment. If it doesn’t, but the patient simply reports feeling better than that would be an example of placebo. However, the science of psycotherapy is still very much in its infancy and so we simply cannot ascertain such things in most (if any) cases. We know empirically that such measurable changes are possible, but we can’t measure them in everyone. We also know that not every type of therapeutic discourse works for every patient (just as not every pharmaceutical works for every patient).

    However, the aim of therapeutic discourse is to illicit a specific result, it can do so, and as best as the field can manage at the moment, it does so in genuine attempts to effect treatment. Thus, I would not call it a placebo. When something is discovered to have little or no therapeutic effect it should be discarded (Freudian analysis has gone mostly the way of the dodo, in my understanding) and usually is. It is just that the field is rather murky and coming to that understanding is often difficult.

  45. pmoran says:

    David: Interesting. Referring to how we’ve complained about The Atlantic article as “frothing at the mouth” is exactly the same sort of “tone” and language you regularly castigate some of us for. You appear to be quite willing to use insulting language and a harsh tone when it suits your purpose; so please explain: Why is it OK for you to use such language and tone to criticize your (mostly) allies but when we do it it’s so very, very counterproductive? This is not an isolated example, either. I recall seeing you do this on several occasions over the last three years.

    We are both big boys, David. I have had to take being dismissed as a “shruggie” or an “accommodationist” and therefore not worth listening to, and it is more insulting than that when this isolated moderately ad hominem phrase is all you seem to have taken as being worthy of a response.

    But that’s OK. I can take it and it will not poison THIS dialogue.

    I know what I know about medicine, and feel secure with the science. Can you take continually being frustrated at the world not behaving in the way that you think it should be behaving?

    I am trying to understand why that is and exploring whether there are equally valid but different ways of looking at it all, but ones that do not require drifting off into New Age nonsense.

    If I am saying anything that is not consistent witt the science, let’s be having you.

    .

  46. @ du2 – I think that your definition of placebo effect may end up being to broad. Most of the definitions I found online to not place an emphasis on placebo being something that is not a drug, surgery or otherwise physical. Here is the mw definition.

    ” improvement in the condition of a patient that occurs in response to treatment but cannot be considered due to the specific treatment used”

    Much of psychotherapy today focuses on recognizing and retraining dysfunctional thought patterns, habits or conditioned responses into more functional ones. This is much like a speech therapist helps a patient to recognize and retrain lip and tongue placement when making a sounds.

    Like many other treatments, there is a placebo effect with psychotherapy, a lift in spirits often created by the hope that therapy can offer some help and the relief of having support in guiding the process, like one finds with the placebo effect from medications.

    But I believe that any long term effects of exposure therapy, cognitive behavior therapy, etc are due to the intentional and specific changes in the patients thought processes and responses to events rather than non-specific effects.

    It seems to me that using a distinction between mental activities and physical activities as the basis for the definition of placebo effects is somewhat arbitrary and undermines the usefulness of the word.

  47. daedalus2u says:

    I think people are missing the point I am trying to make. Yes, “placebos” don’t have specific active effects. But placebos do have physiological effects, that is they do affect the physiology of the individual that is experiencing the placebo effect. The physiology of the “placebo effect” is not in the placebo, it is in the physiology of the individual that is experiencing it.

    Defining “placebo” as something inactive turns every CAM treatment (when they work) into non-placebos. If acupuncture “works”, that is it produces therapeutic effects, then it is not a “placebo” (according to the definitions that people want to use). If toothpicks are equivalent to acupuncture, then toothpicks “work too”, and toothpicks are not a placebo (because they work).

    You can’t define non-placebo as something that works better than placebo without defining what “placebo” means.

    If you require an understanding of the physiological processes that are involved to determine if something is a placebo or not, that is unsatisfactory because the default is unknown. Without knowing for sure that there are no energy fields that Reiki taps into, how can one be sure that Reiki is a placebo?

    There are effective placebos, psychotherapy is an effective placebo. Psychotherapy produces therapeutic physiological changes that are not mediated through drugs, surgery or other physical effects.

    People have to get away from the idea that placebos don’t do anything. Placebos do have physiological effects. That is why placebos are essential in double blind studies. If placebos had no physiological effects, then the placebo arm of a trial would be “the same” as a no-treatment arm. The placebo arm is different than the no-treatment arm, placebos have physiological effects.

    The mechanism(s) by which placebos have physiological effects remain unknown. If you want to use the term “placebo”, it needs to have a specific meaning, and not a meaning that changes depending on what you want it to mean.

  48. daedalus2u says:

    Trying to use a “mental” vs. “physical” division is unsatisfactory because all mental effects are only due to physical effects of physiology. Psychotherapy changes the physiology of the brain and results in neuronal remodeling. All brain activity does too.

  49. du2 – If my reading of your comments is correct and we use your definition of placebo, we can not test for effective psychotherapy techniques, because no technique will be “better than placebo”.

    Yet, it appears to me that science has found that some psychotherapy techniques “work” better than others for particular psychological symptoms. This is unlike something like acupuncture, where a toothpick and a needle produce the same relief.

  50. DU2 “Trying to use a “mental” vs. “physical” division is unsatisfactory because all mental effects are only due to physical effects of physiology.”

    I don’t think you are getting what I’m saying. CBT is to the brain as Physical therapy is to the muscles. You use your brain in a certain way, it changes. You use your muscles in a certain way, they change.

    Of course there is a physiological component to both and of course there is also a cognitive process to both (I am not suggesting a ghost in the machine unrelated to physiology that enables the cognitive process.) This is why I am saying that the distinction that you are using between a physical therapy and a psychological therapy, defining the first as not-placebo and the second as placebo seems arbitrary.

    Also, I haven’t seen anyone suggest that placebo’s don’t do anything.

  51. wales says:

    Daedalus – Thanks for the link, I will take a look at it.

    This paper is informative on the subject of magnetophoretic mobility of blood.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302830/

    I have seen multiple references to the fact that oxygenated blood is diamagnetic and deoxygenated blood is paramagnetic. However I found it curious that the authors of this paper also mention oxygenated blood’s possible paramagnetic properties “our methods should allow us to address in the near future the question posed by Cerdonio (Pauling and Coryell, 1936b; Savicki et al., 1984; Cerdonio et al., 1978, 1985) about oxygenated hemoglobin’s possible paramagnetic contribution.” Haven’t had time yet to further research any updated findings in that regard.

    In any case, this study showed that the red blood cell velocity increases significantly when very high magnetic fields are applied. “We consider that this work contributes to our current understanding of the influence that the exposure to extremely high magnetic fields could have in physiologic systems. Although deoxygenated RBC migration velocity is zero when exposed to a homogeneous magnetic field, this velocity is significant when exposed to high magnetic gradients, as the ones generated in the proximity of highly sophisticated MRI devices.”

    Tao claims that the decreased viscosity persisted for several hours after the magnetic field was applied for only a one minute duration, which implies that the chains don’t immediately disintegrate.

    Fascinating subject, to me anyway.

  52. daedalus2u says:

    wales, I am quite sure the idea of chains of blood cells due to application of a magnetic field is wrong. The effect of magnetic field on changes in blood viscosity may be correct, but it is not due to magnetic chaining of red blood cells.

  53. daedalus2u says:

    Michelle, most placebos are not about “exercising” mental functions, they are about poking people with needles, waving hands over them, mumbling words to some supernatural agent, or administering magic water.

    People doing acupuncture, reiki, prayer, or homeopathy are not trying to exercise the mental functions of their victims, other than to make them more susceptible to what ever magical thinking they are invested in.

    Any two treatments can be compared, even two placebos can be compared. Toothpicks and needles both work for acupuncture, in some studies toothpicks have worked a little better. I suspect that toothpicks do actually work better because they don’t break the skin, and breaking the skin activates some fight-or-flight pathways that are the opposite of the placebo effect (according to my conceptualization of it).

    If you want to understand how a placebo treatment works, how it is having therapeutic effects and what physiology is being affected by it, you have to understand the physiology of the placebo effect. Trying to understand acupuncture and toothpicks via the idea of meridians and chi isn’t going to work because there are no such things. Trying to understand the effects of homeopathy by trying to understand the memory of water isn’t going to work because there is no memory of water.

    If you want to study the placebo effect, first you have to define what it is, and use a definition that is consistent with what is generally known about what are generally considered to be placebos. Then with that definition, you can divide treatments into placebo and non-placebo treatments and start studying the commonalities of the placebo treatments, and what physiology must be involved.

    What is it about psychotherapy that makes it not a placebo according to how you want to define placebo? How is reiki a placebo by the same definition?

  54. wales says:

    Well, perhaps the problem is purely semantics. When Tao refers to RBC “chain” perhaps he refers to the following phenomenon:

    It is known that RBC’s commonly form “rouleau” aggregates, RBCs aggregated like a stack of coins. As velocity of blood flow increases, the following occurs:

    “as the shear rate increases, RBC rouleau tends to break up. Individual RBCs also deform, elongate, and align with the streamlines.”

    http://www.tam.northwestern.edu/wkl/_wkl/pdf/Rheology%20of%20Red%20Blood%20Cell%20Aggregation%20by%20Computer%20Simulation.pdf

    It seems that the deformation, elongation and alignment with streamlines is what is being referred to by Tao’s “chain” effect.
    There are some nice graphics of this effect in the cited paper, showing the horizontal “coin stack” of RBCs morphing into more of a vertical “chain”.

  55. wales says:

    Anyhow, blood rheology appears to be complex and multi-factorial. The authors of the above cited paper point out the limitations of existing models of blood rheology.

    Perhaps the application of a magnetic field increases the velocity of blood flow, leading to the vertical “chain” effect.

    In any case, I appreciate the input. Must move on for the moment.

  56. wales says:

    Make that “BECAUSE the application of a magnetic field increases the velocity of blood flow…”

  57. wales says:

    wow, my apologies, up above I meant to say that the VERTICAL “coin stacks” morph into “horizontal” chains…..too much multitasking.

  58. JPZ says:

    @d2u

    Pardon my ignorance, but I am really missing the point you are trying to make about placebos. A “placebo” is defined by the “treatment” used in the trial, i.e. you cannot call something a placebo without first defining the treatment. The placebo should be identical to the treatment in every respect except for the active ingredient. Where that is not possible or ethical, one makes compromises in the composition of the placebo that can affect the blind or outcome. Or, one can forego the placebo and do a head-to-head comparisons of treatments; therefore, the trial does not measure how much of therapeutic effect of either treatment is due to the placebo effect.

    If I want to compare drug X to acupuncture or CBT to prayer, I am doing a head-to-head comparison because both arms are hypothesized to work. If I want to compare acupuncture with needles along meridians to acupuncture with needles in random placements, I am attempting a placebo control.

  59. pmoran says:

    Daedalus: People have to get away from the idea that placebos don’t do anything. Placebos do have physiological effects.

    Never direct physiological effects. All studies of placebos show that they require preliminary psychological conditioning of some kind. This is why a pharmacologically active biofilm doesn’t fit comfortably into present concepts of placebo..

    If the word placebo is being used in the context of how CAM practitioners might produce beneficial outcomes, then, for want of a snappier term, it would be better to refer to” non-specific influences within medical interactions including those related to placebo use”, for this is a vastly more complex therapeutic environment.

    Those influences may be as diverse as the force of the practitioner’s personality, keeping the patient so busy with complex regimes that they get distracted from being sick, finding spurious “answers” where others failed, having an entitlement under the cloak of “holism” to pry deeper into a patient’s personal life than many patients will tolerate elsewhere, and superior opportunities for patient-practitioner interaction through the operation of treatment programs such as spinal manipulation or acupuncture..

  60. daedalus2u says:

    Treatments that don’t have “direct physiological effects” is very close to what I am trying to use as a definition. But that only applies to the immediate “trigger”.

    Once a “placebo effect” is triggered, presumably at some point it is the plain vanilla “normal physiology of healing” that produces what ever the positive therapeutic effects are from that placebo treatment (it certainly isn’t some mystical woo-woo magic). But by what mechanism does an organism that is conditioned to respond to a placebo trigger that placebo effect, and how do the therapeutics effects triggered by the placebo effect get activated? They are all very complex and involved physiological pathways, there must be very complex and involved physiological control pathways to regulate them.

    The placebo effect doesn’t need to be complex to trigger all these complex healing pathways, it just needs to “turn on” the complex healing pathways which then regulate themselves in all their complexity. That so many different placebos all seem to “work”, implies that the placebo effect itself, the one that triggers the plain vanilla “normal physiology of healing” pathways doesn’t need to be complex because all the different woo-woo magic CAM treatments trigger it. The common denominator of those placebo treatments is likely pretty simple and fundamental to physiology (and from deep evolutionary time if it regulates healing). That simple trigger isn’t in the CAM treatment, it is in the physiology of the organism.

    But what is an indirect physiological effect? How is that different from a direct physiological effect and how and why are those useful distinctions to make? Are the effects of psychotherapy direct or indirect? How does one distinguish the direct and indirect effects of various treatments ? I can’t measure “direct” and “indirect” physiological effects because they are not well defined.

    Does a mother’s “kiss it and make it better” have direct or indirect effects? To me, a mother’s kiss is a placebo (the archetypal placebo), but I think it is not clear that it requires any conditioning on the part of the infant to exhibit it. It may be hard wired. I am pretty sure that sugar on the tongue is a hard-wired placebo effect (for infants). It mimics the physiology of nursing (application of something sweet to the tongue) and if an infant is being held by his/her mother and she feels safe enough to produce milk, then as far as the infant is concerned, everything is right with the world.

    I want a definition of what a placebo is that is clear and unambiguous, which definition doesn’t change for different individuals. I would like the definition of “direct physiological effects” to only include things that can be measured or are known to actually exist, so that homeopathy, reiki, and meridian balancing cannot be considered to be “direct”, but yet leave things open for new discoveries, but not so open that it can be used to justify nonsense.

    I don’t like the term “non-specific effects”. We don’t know if the effects are specific or not, the effects are simply unknown. I am also trying to limit this to only treatments that actually have positive physiological and therapeutic effects. Distracting the patient, or bullying the patient into agreeing that the patient is feeling better is not within what I consider to be the placebo effect.

    I agree with you that a pharmacologically active biofilm is not a placebo. I think what the biofilm does is lower the threshold for activating the placebo effect. If the threshold is lowered enough, it can activate itself spontaneously. If all the placebo effect is doing is turning healing back on, then if you are fully healed, there is nothing more a placebo can do for you.

  61. nybgrus says:

    @daedalus:

    What is it about psychotherapy that makes it not a placebo according to how you want to define placebo? How is reiki a placebo by the same definition?

    I would say it has to do with proposed mechanism. I think JPZ said it well that you must define placebo against treatment. Reiki is not a placebo – it is an attempt at an active treatment. If you were to compare reiki to say an opioid for pain relief, you would be comparing two active treatments. However, when you look at the proposed mechanism of each, one can see the reiki is much less credulous and you can then try and compare it against “placebo” using its proposed mechanism of action – i.e. I wave my hands over someone and a reiki master does the same. My treatment would be placebo since I am mimicking the reiki master but have no ability or intent to manipulate energy fields, whereas he does (or at least claims to). If the results of our “interventions” produce the same level of results, then we can say that reiki’s effects are mediated via placebo effect since there is no active intervention separating it from me randomly waving my hands over someone.

    The same goes with acupuncture – when the central claim is needles in meridians to manipulate chi, if you compare that to an active treatment arm, you are comparing two treatments. If you want to get to the meat of the effect, you must then compare acupuncture to pseudopuncture (i.e. not in prescribed points). If the effect is the same you now know that the points don’t matter and the meridian theory is BS. Then you can compare it to sham acupuncture (toothpicks) and realize that the needles themselves don’t matter either. Now that you have removed all elements of what is proposed to be active in the intervetion and the effect remains, you can say it is mediated through placebo effect.

    I agree that “non-specific” is probably not good terminology – it is more accurate to say “unkown.” Once you have a situation, like acupuncture, where there is nothing left but “unkown” or “placebo” mediating the effect of the intervention, then you can safely say that it is not ethical to knowingly administer or prescribe such an intervention to a patient (which is where it seems that pmoran disagrees with me).

    Additionally, my understanding is that placebo effects have not been demonstrated to objectively improve outcomes, only subjectively and that the effects are transient. So any physiological changes are related to things like endorphin release or activation of pain modulation pathways (the same way a mother’s kiss works – by activating the higher order inhibitory neurons in the pain perception pathways).

    So to tie it back in to psycotherapy, if the effect of it is to actually remodel neurons, which is inline with known mechanisms and effects, and is intended for that outcome (i.e. depression gets better because we are trying to make depression better) then that would not be a placebo effect – that would be an intended and direct effect. Of course, as I said before, since the measurements of that are difficult if not impossible at the moment, we are relegated to much trial and error, differing effect sizes, and subjective response assessments to gauge the efficacy. This means that at least some (maybe more) of psycotherapy is indeed placebo, but that at least some is not. The intent is to not be, and the science behind it is attempting to suss out which is and which is not.

    And as I have also said, if you don’t know your treatment (say CBT) is a placebo and your intent is to actively treat then that is ethically justifiable – you are merely working within the limits of knowledge. But once something is identified as placebo (such as has been done with acupuncture) then you are ethically bound to discontinue using it and either substitute something else that works or attempt to find something that does.

    Of course, pmoran would like to tell me that the science doesn’t show acupuncture to be a placebo, but I and many others here disagree. Or perhaps it is that he feels we can be a bit wishy washy when the science is complex to take advantage of potential placebo effects to make up for where science based medicine is lacking. This is also something I find untenable.

  62. daedalus2u says:

    What if someone who is not versed in reiki skillz waves their hands over someone, is that a placebo? Is it a placebo if the person is asleep? If the person being treated thinks it is a placebo? If the person doing the hand waving thinks it is a placebo? If the person being treated has his/her vision obscured and an animated manikin is used for the treatment? If the person knows/doesn’t know it is a manikin?

    Making the definition of “placebo” contingent on the mental state of the various participants is unsatisfactory. Making the definition of “placebo” contingent on the intent of which physiological effect the treatment is trying to induce is also unsatisfactory.

    Having a treatment change from being non-placebo to being a placebo is unsatisfactory. We may not know if a treatment is a placebo or a non-placebo and we can do experiments to find that out. According to your proposed definition reiki by a reiki master is a non-placebo until that specific reiki master is tested against placebo and is found to be no better than placebo, for that patient, unless the placebo “works too!”, which according to your definition makes it not a placebo.

    If I attempt to actively treat a headache with a sugar pill, is the sugar pill a placebo? According to your definition it can’t be because it is being used to actively treat something. There is no known physiology by which a sugar pill would treat a headache, but if only intent is required, then there are no placebos.

    Psychotherapy does change long term mental activity. Therefore we know it must cause neuronal remodeling. All mental activity is mediated through neuronal activity, all changes in mental activity must be caused by changes in neuronal activity which are produced through neuronal remodeling.

    Thinking causes neuronal remodeling. The newly remodeled brain now has a memory of the thoughts it had a few seconds ago. That change can only occur through physical changes in the brain, those physical changes constitute neuronal remodeling.

    Placebo effects have been demonstrated to have measurable physiological effects. In one of the papers I cite in my blog post on the placebo effect they had instrumental measurements of increased gastric motility following administration of a placebo and decreased gastric motility following administration of a nocebo, the same substance in both cases.

    When statins were developed to reduce cholesterol, it was reasoned that they would work because they inhibited a step in the cholesterol synthesis pathway. Low and behold statins did reduce cholesterol, but the activity of the enzyme that was supposedly inhibited was upregulated and was more active than in the absence of the statin. Did finding out that the statin didn’t work by the expected physiological pathway turn it into a placebo?

    How do you distinguish between acupuncture needles working and toothpick working? At one time acupuncturists thought that needles were required, but now they have made the discovery that toothpicks work too. How do you distinguish between both being placebos and neither being placebos? According to your definition of intent of treatment, it all depends on the intent of the person doing the treatment. If I build a mechanical acupuncture robot, does it depend on the intent of the programmer?

  63. JPZ says:

    @d2u

    “Making the definition of “placebo” contingent on the intent of which physiological effect the treatment is trying to induce is also unsatisfactory.”

    I am not entirely sure what you mean, but I am making a wild guess that you may be confusing “ineffective” with “placebo.” If I hypothesize that a sugar pill effectively treats a headache, I have to specify what is the active ingredient/factor in the sugar pill that effectuates the outcome. Then I would design a placebo that is indistinguishable in every way from the sugar pill except for the active ingredient/factor, e.g. type of sugar maybe.

    Maybe a different tack will help, a placebo is meant to subtract all elements of a treatment from the study outcome except the active ingredient/factor. In animal studies, this can include sham operations or other invasive methods. The point is to prove that it wasn’t the shape, size, form or other aspect of the treatment that created the outcome, only the active ingredient/factor.

  64. pmoran says:

    Daedalus2 Does a mother’s “kiss it and make it better” have direct or indirect effects? To me, a mother’s kiss is a placebo (the archetypal placebo), but I think it is not clear that it requires any conditioning on the part of the infant to exhibit it.

    When I used the phrase “preliminary psychological conditioning”, I was not thinking of Pavlov. “Mummy will kiss it better?” can induce the required state of expectancy or suggestibility..

    I want a definition of what a placebo is that is clear and unambiguous –

    WOuld it help for you to think in terms of placebo responses, not placebo effects. In a strictly therapeutic sense, the placebo “does” nothing,. The patient is simply reacting to the whole therapeutic experience. Certain qualities of the placebo may influence responses, but again via psychological processes..

    I don’t like the term “non-specific effects”. We don’t know if the effects are specific or not, the effects are simply unknown.

    I actually used the term “non-specific influences”, which includes placebo -related phenomena, and describes what we mean for the context I set i.e. all possible influences within therapeutic interactions that are not intrinsic to the treatment rituals used. You could substitute any other treatment ritual and you would have the same responses, so long as it had similar qualities in terms of mystique, invasiveness, intensity etc.

  65. pmoran says:

    Nybgrus: Of course, pmoran would like to tell me that the science doesn’t show acupuncture to be a placebo, but I and many others here disagree.

    I merely maintain that it is stretching the practical medical significance of the placebo/non placebo divide to its limits when a designated placebo contains elements that can plausibly can have (unintended) therapeutic value beyond the usual expectancy responses, such as distractant and counteriritant effects, along with a program of enforced relaxation and “time outs” — AND it also produces effect sizes within controlled trials that rival that or exceed that of some pharmaceuticals. (I say this being aware of the likelihood that some of that is bias, but pointing out that there are other factors operating in such studies that will tend to inhibit patient responses.).

    So, let’s not aggravate matters with hubris, pretending that such a decision represents some peak of intellectual achievement and ethical responsibility. It is a very close run thing on all grounds, and there is little basis on which to look down on those who might choose differently.

    So, lr perhaps it is that he feels we can be a bit wishy washy when the science is complex to take advantage of potential placebo effects to make up for where science based medicine is lacking. This is also something I find untenable.

    That’s fine, no one is making you do anything. The question is to what lengths you are prepared to go to to poison this well for others.?

  66. du2 -I have been basing my ideas of placebo from definitions of placebo effect. Here’s one
    “placebo effect – n.
    A beneficial effect in a patient following a particular treatment that arises from the patient’s expectations concerning the treatment rather than from the treatment itself.” The American Heritage® Medical Dictionary

    also
    “a physical or emotional change occurring after a substance is taken or administered that is not the result of any special property of the substance. The change may be beneficial, reflecting the expectations of the patient and often those of the person giving the substance.”
    Mosby’s Medical Dictionary, 8th edition. © 2009, Elsevier.

    I crux of the definition seems to me whether the results arises from the patients positive expectations of the treatment or as a result of the actual intervention.

    Yet you say “Making the definition of “placebo” contingent on the mental state of the various participants is unsatisfactory. Making the definition of “placebo” contingent on the intent of which physiological effect the treatment is trying to induce is also unsatisfactory.”

    Upon reading your comments, it’s beginning to look like you don’t really like the established definition of placebo effect, because it does not meet your needs.

    Perhaps you need to look for another word to suit your purpose?

  67. evilrobotxoxo says:

    One thing I’d like to point out is that “placebo” arms of clinical trials are actually measuring more than just the placebo effect as you guys are discussing it here. One part of it is genuine improvement in the physiological condition due to nonspecific treatment effects, which is what you guys are discussing. Another part is bias in patient reporting of symptoms after receiving “treatment,” which is another component of it. A third effect that is particularly relevant in trials of antidepressants, for example, is the natural time course of the condition. Many conditions wax and wane over time, and people are enrolled in trials at a time when the condition is doing worse, then they get better spontaneously. “Placebo” arms of trials are really just measuring nonspecific effects, one of which is the placebo effect per se. In the case of antidepressant trials, the limited data that exists suggests that most of the effect in the “placebo” arm is not due to the placebo effect, but to other nonspecific effects.

  68. woo-fu says:

    @daedalus2u

    In my experience, psychotherapy is essentially an educational process generally performed one-on-one. In psychotherapy the client is prompted to observe, question and analyze individual and social behaviors (not subjective) as well as the client’s feelings (subjective) about those behaviors. Where there are concerns or deficits, psychotherapy can allow the client an opportunity to develop new skills for both self-management and social interaction, again an educational process.

    This is where I have problems with your definition of psychotherapy as placebo. Psychotherapy is no sugar pill. You state, “all mental effects are only due to physical effects of physiology” (remodeling) and then go on to state, “Thinking causes neuronal remodeling.” This seems to be a “chicken or egg” proposition.

    Both traditional classroom education and psychotherapy are intended to prompt critical thinking skills. Learning does indeed have effects on the brain; the best examples I’ve seen regard stroke survivors. However, it seems, if I applied your definition, the entire process of education might be defined as a placebo. Of course, that’s only if I understood your position as you intended, which I may not have done.

  69. daedalus2u says:

    What I am trying to get at are the physiological effects of placebos, how they are triggered and what can they do. I am not interested in changes in the belief states of individuals. If there are no actual physiological effects, then there are no effects, no medicinal effect and no placebo effect. I appreciate this is a special case and usually all medical treatments have some of both and all CAM treatments have only non-specific effects.

    I think we are all agreed that anything that has any effect on any organism only does so by affecting the physiology of that organism.

    If “non-specific effects” have an effect on the therapeutic outcome of a treatment, then those “non-specific effects” are affecting the physiology of that organism.

    If “everything else but the pharmacologically active drug” has an effect on the therapeutic outcome of a treatment, then “everything else but the pharmacologically active drug” is affecting the physiology of that organism.

    What I am trying to get at is the common physiology that is being triggered by those “non-specific effects” and consider it independently of the “specific effects” of a particular treatment. This is difficult to discuss semantically because what is a “specific effect” and what is a “non-specific effect” is (largely) in the eye of the beholder. To the acupuncturist, poking someone with needles has a “specific effect”, the same “specific effect” that poking someone with toothpicks has, so to the acupuncturist they both are acupuncture.

    All treatments have non-specific effects. Some treatments, in addition, have specific effects. What I am trying to get at are the “specific effects” of “non-specific effects”. In other words, what is the common and specific physiology triggered by the non-specific effects of treatments.

  70. daedalus2u says:

    Woo-fu, I would say that being taught is a placebo in the same way that being bullied is a nocebo. Being bullied certainly has physiological effects. Those effects are not mediated via pharmacology, they are the normal human response to certain types of social treatment.

    The difficulty in discussing this is that there is no clear distinction between things that affect physiology in everyday life, for example seeing something and remembering it only happens because of physiology. Seeing something and becoming frightened, or becoming anxious only happens because of physiology too. Seeing something that causes PTSD only happens because of physiology too.

    The physiology of the placebo effect is always happening. When you are healthy and not in a fight-or-flight state, you are already in a state where healing is happening. When you get into a state where healing is compromised, because physiology has diverted resources elsewhere, as in fight-or-flight, then to resume healing those resources have to be re-allocated back to healing.

    The only way those resources can be re-allocated is via physiology, but it is the physiology of the control of physiology that needs to be changed. One way to think of it is like a “healing thermostat setpoint”. When you need to run from a bear, your “control of physiology” turns the “healing thermostat” down, so you use fewer resources for healing while you are trying to escape. The resources you have diverted from healing might save your life by giving you a slightly faster escape. Once you have escaped, your “control of physiology” needs to re-allocate those resources or your healing setpoint stays turned down. If there is no injury during your escape from the bear, you might not even notice that your healing setpoint has been turned down. But if it doesn’t get turned back up, eventually you will notice because wounds will heal very slowly, the normal wear-and-tear accumulates, and you start to get degenerative diseases.

    If you are in a state where the healing thermostat is turned down, that healing thermostat can be turned back up via multiple processes. The physiology that turns the healing thermostat back up is something that would be indistinguishable from the placebo effect. The “perfect” placebo does nothing except turn on appropriate levels of healing. Anything that did turn on the appropriate level of healing would act as a placebo.

  71. pmoran says:

    Daedalus2:Daedalus2:What I am trying to get at is the common physiology that is being triggered by those “non-specific effects” and consider it independently of the “specific effects” of a particular treatment.

    There isn’t any “common physiology” to talk about. The NSEs infuence perceptions rather than physical or physiological processes, unless youhave in mind the barely understood brain processes that finally control a lot of what we experience. (Those gastric mobility changes are initiated in the brain and mediated by the autonomic nerves — no mystery there).

    There is also no true “healing”, a word that to medical science means no more than the repair of damaged tissue or wounds. With placebo/NSE/responsive complaints there is no damaged tissue and nothing to “heal” in any true sense, althougheven in destructive diseases there may be associated subjective symptoms that will respond to suggestion or expectancy.

    CAM has co-opted the word healing to cover “getting better for any reason”, adding nice, soothing, quasi-spiritual, patient-empowering overtones until there is no longer has any hard core of meaning.

    To my mind the simplest form of placebo effect is that having taken what we expect to be effective action about a medical problem we then get on with our lives and pay less attention to symptoms. We feel better, but nothing has changed.

    Likewise illness can be simply due to too much focus on sensations and anxiety about essentially harmless symptoms that are prevalent within the normal population. So simple reassurance or being under confident care can have a powerful effect on symptoms, without affecting any of the lower level physiological processes that you need in order to get your NO theory of placebo off the ground..

  72. nybgrus says:

    I think I can safely say that you and I completely agree on something pmoran.

  73. daedalus2u says:

    PM, what basis do you have for saying there is no common physiology? Without knowing what physiological processes are triggering each different thing, by what basis do you know that they do not share commonality?

    When I say “healing”, I mean exactly what you mean, the repair of damaged tissues or wounds.

    Yes, what I am talking about are centrally regulated healing control mechanisms. Yes, what I am talking about is not even barely understood, it is not even recognized as something that even exists or that can be understood except by a very few researchers. But we know that there are centrally located control mechanisms that regulate healing. We know that high doses of corticosteroids slow healing. We know that when people are under stress, any wounds that they have heal more slowly. In many of these cases wounds still heal, they heal with “high fidelity”, they simply heal more slowly.

    We know that healing is a complex process that must be idiosyncratic to each tissue compartment because each tissue compartment is comprised of different cell types. Healing of the skin, muscle, vasculature, bone, liver, and so on, involves many different cells and cell types which must undergo cycles of proliferation and differentiation in very complex but extremely well regulated pattern(s). Some of that regulation is local, some is global. How the global regulation modulates the local regulation is what I am trying to discuss.

    When many complex and idiosyncratic processes (healing in multiple tissue compartments) are regulated together, up and down in sync, presumably at some point there must be a single common signal that triggers all the other control pathways that then work together in sync.

    When a complex process of many steps proceeds with high fidelity but at different rates, the presumption is that the complex process is being controlled to proceed at different rates. If the process had somehow gone “out of control”, it would not proceed to produce a high fidelity result. If a high fidelity result is produced, then the “control” of the complex process is being maintained.

    We know that healing requires resources, substrates to make ATP, substrates to make proteins, to clear damaged tissues, to phagocytose debris. We know that the capacity of the body to deliver and utilize those substrates to damaged tissue is limited. We know that the rate of healing is not uniform, that is it proceeds at different rates depending on numbers of other things.

    When a physiological process that requires resources is self-regulated to be slower, my presumption is that physiology is self-regulating that process to be slower so as to consume resources at a slower rate.

    Healing of damaged tissue is an important physiological task. If physiology is diverting resources away from healing to something else, that something else must be something that physiology considers to be more important.

    In terms of treatments that accelerate healing, what type of treatment is the used of nestlets?

    http://www.ncbi.nlm.nih.gov/pubmed/19436750

    Did the nestlets merely influence the perceptions of the mice? Or of the researchers? Or did they trigger a central pathway that upregulated the rate of healing? I would call the nestlets a placebo because they mediated a therapeutic effect (faster healing) but didn’t mediated it through a direct pharmacological effect.

    Oxytocin is released during positive social situations. The sensation of being reassured that one is under competent medical care will release oxytocin. Oxytocin, whether endogenous or exogenous does cause the release of NO. The effects of endogenous oxytocin released through non-pharmacological interventions (nestlets or reassurance of competent care) is what I consider to be a placebo effect. Injection of oxytocin would be a pharmacological intervention even if the same oxytocin mediated pathways were activated.

  74. JPZ says:

    @d2u

    OK, I think I am gaining a few insights from your last few posts, but I ask that you forgive me if I mischaracterize your POV. I can see that you have an interest in the poorly understood physiological processes surrounding spontaneous improvement in patients who do not receive pharmacologically active treatments.

    As evilrobotxoxo pointed out, a significant amount of the “placebo effect” may be regression to the mean, reporting bias, etc. – none of which have anything to do with poorly understood physiology. We understand the statistical nature of regression to the mean and other factors very well – recruit sick people, don’t hurt them, and more of them are healthier at the end of the study.

    Is there more than that? Maybe, I really don’t know despite years of wrestling with placebo effects in clinical trials. It would be difficult to parse out the statistical probability of spontaenous improvement due to known mechanisms and probability from the postulated self-invoked healing mechanism inspired by the placebo treatment. It is not a bad area of research to pursue, if you are so inclined.

  75. daedalus2u says:

    That is ok, I am just trying to educate and get people to understand where I am coming from. I think if they do, they will reach the same conclusions that I have.

    In trials of acupuncture, “standard care” doesn’t do as well as real acupuncture and sham acupuncture. The differential between standard care and the two acupuncture legs isn’t regression to the mean or other artifacts, it really does appear to be a real physiological effect.

    What ever that physiology is, we know it is not some magical effect of needles or toothpicks. At some point along the path from acupuncture woo-woo to healed patient there has to be physiology that does something to regulate healing to be faster. That something is what I think I can tap into with my nitric oxide bacteria.

    I think if that something is activated by my bacteria, there won’t be a something to be activated by acupuncture woo-woo or any other kind of woo-woo.

  76. pmoran says:

    PM, what basis do you have for saying there is no common physiology? Without knowing what physiological processes are triggering each different thing, by what basis do you know that they do not share commonality?

    When I say “healing”, I mean exactly what you mean, the repair of damaged tissues or wounds.

    Then I suspect you are approaching the placebo matter from the wrong end and with false assumptions.

    Have you looked at everything we know about placebo influences? When can they occur? How quickly? What induces them?

    Among the earliest observations of placebo was that severe post-operative wound pain can be relieved by a saline injection, as quickly and sometimes as effectively as 20 mgm of morphine.

    That is just one critical observation that does not seem to fit your conceptual framework. It is very difficult to explain that in terms of influences on wound healing.

  77. woo-fu says:

    @daedalus2u

    Thanks for breaking down your position.

    Let me see if I’ve got it down correctly. You’re defining placebo as something effecting a positive change without direct pharmacological or, I’m assuming, without direct mechanical (setting bones, for ex.) method of action. By this definition, any effect (including learning) from therapy, educational seminars and other social interactions could then be defined as a placebo or nocebo effect, depending on a positive or negative outcome. Do I have that right?

    I think that might be to broad a definition to be workable; however, I can see the value of the comparisons. I would suggest rather than using the terms “specific effects” and “non-specific effects” for your argument, use direct and indirect. There might be a little less confusion that way.

    The link to the rat’s nest v. oxytocin study was intriguing. It makes plenty of common sense. Shelter is one of the basic needs. Growing up in isolation then finding shelter in the habitat should be an immediate comfort. I might hypothesize that the perception of the habitat triggered the chemical cascade that we associate with well-being. I suppose in that case the perception of the nest would be exerting an indirect effect. And since there is real physiological change with respect to the rat’s own neurochemistry, I see how that would fit your definition of placebo.

    Could indirect effects which seem to trigger the body’s own pharmacy into production be explained by the still mysterious action and function of astrocytes?

  78. DU2 – It appears to me that you are interested in how psycho/social interactions may effect physiology and therefore the body’s ability to heal or respond to sickness.

    That is a very interesting endeavor, but I think that the use of the words placebo/placebo effects may be causing more confusion than clarification.

    It seems to me that the placebo effect would be one sub-heading under a broader heading of something like “psycho/social interaction” or even (cringe) “Mind/Body interaction”…more reading into the topic may provide a more useful vocabulary.

  79. daedalus2u says:

    PM, I have tried to read as much as I can get access to on the placebo effect. I have read a lot of what is available, the quality of it is quite mixed.

    To me, lumping together mistakes and artifacts of perception in with the physiology of the placebo effect is unfortunate because it adds a lot of noise to what I am trying to study. I appreciate that many people don’t want to accept that there is physiology behind the placebo effect and that there are only errors of perception. This idea really does not fit the data in the literature. The data on trials of real, sham and no acupuncture clearly show effects of real and sham acupuncture. One can take the approach that either both are placebo or neither is placebo, but because both are different from no treatment, real and sham acupuncture are doing something and not just clouding the patients’ and clinicians’ perceptions.

    The lumping together of data on the effects of placebos on very disparate disorders which result from quite different underlying physiology is also unfortunate. There is little commonality between the physiology of cancer and wound healing. Something that accelerates wound healing may also accelerate cancer progression, or it may not depending on the genotype of that particular cancer and what growth factor receptors it expresses. There isn’t an a priori reason to suppose that there is commonality in the restorative pathways in diverse disorders except in resource allocation. If any tissue compartment or physiological process is “starved” of resources, eventually it will break down and not do well.

    I am coming at the placebo effect from physiology, and how and why evolution configured physiology to exhibit what we call the placebo effect. I don’t think there is another way to come at it. I think that thinking about the placebo effect as a “top-down” effect is the wrong approach. Healing comes from deep evolutionary time. Control of healing comes from that same deep evolutionary time. You can’t have “healing” without also having “control of healing”.

    Injected saline having pain relieving effects is completely consistent with my conceptualization of the placebo effect. Those first observations were in the context of battlefield casualties, where doses of morphine required for pain relief were much less than were needed for similar severity wounds received in accidents occurring in civilian circumstances.

    My explanation is that being in a war, being in a battle, being shot at or being blow up, or having a known risk of death is going to trigger the fight-or-flight physiological state. A civilian in a car accident doesn’t have the same pre-injury experiences to trigger the fight-or-flight state and doesn’t have the time before injury to very robustly adapt the whole of physiology to that fight-or-fight state. When the battle is over and the injured soldier is receiving care, the soldier knows that he/she can stand-down from the fight-or-flight state needed when in a battle.

    Pain is a signal that indicates ongoing damage and reduced capabilities of that tissue compartment. It is a signal telling an organism to get out of harms way and to seek help for injuries. When those tasks are accomplished, ongoing pain is not needed. It makes sense to me that after a battle the need for pain relief is less than after an automobile accident with the same wound severity.

    Woo-fu, yes. I appreciate that many don’t like the definition of placebo that I want to use, they want the term to have the connotation of “doing nothing” or “useless”, or “not effective”. But there are drugs that are ineffective too, and they are not called “placebos”. An injection of saline on the battlefield is effective and is properly called a placebo.

    I don’t want to get into any kind of terminology that supports or implies a mind/body dualism. There is no such thing, there is only physiology. Treatments like psychotherapy are having effects on the brain. We know that because we know there is change in behaviors, in affect, in symptoms of neuropsychiatric disorders and so there must be changes in the brain that instantiates those behaviors even if we can’t measure the changes other than behaviorally. Psychopharmacology changes behaviors too, so we know drugs are having effects on the brain that we mostly can’t otherwise measure.

    I don’t even begin to understand what astrocytes do.

  80. DU2 – My understanding is that within CBT “the mind” usually represents our self-concept, thought processes, … all that “mind” stuff that we are aware of that makes up our “self”. CBT is based on the idea that the way you use your mind and behave effects your mood and habitual use of mind/behavior patterns effect your brain (remodeling). There is no denial (in CBT) that the “mind” is the result of a physiological process. In fact, awareness of the physiological process and setting up a distinct boundary between “the mind” and “the brain” is one strategy in CBT.

    One key phrase in a therapeutic method for anxiety disorders is “It’s just my brain that’s making me feel this way.” This is an acknowledgment that the anxiety that we may be feeling at a particular moment is probably a conditioned physiological response, rather than a considered (mind) response to a real danger. In other words, our brain is in the habit of sending us anxiety messages when we are exposed to a certain stimuli (loud noise, spider, etc) but we have a choice of how we use our mind to respond to that anxiety, AND how we use our mind to respond to the anxiety will effect the conditioning our brain receives.

    Does that make any sense? What I’m trying to say is that the definition of “mind” is conceptual rather than physical…but it is still a very useful concept.

  81. nybgrus says:

    One can take the approach that either both are placebo or neither is placebo, but because both are different from no treatment, real and sham acupuncture are doing something and not just clouding the patients’ and clinicians’ perceptions

    But treatments like acupuncture only do well for conditions that are perceived. In a piece written by Gorksi the effects on osteoarthritis are noted and subjective pain levels have decreased whilst objective level of function remained exactly the same. I have yet to see any instances of acupuncture or any placebo for that matter actually accelerating wound healing objectively (i.e. length of time required for a laceration to heal). I reckon there aren’t too many rigorous studies in this area.

    However, that I why I said above that the placebo is a transient and subjective effect, not a permanent or objective one. Pain perception is more than just nociceptors sending a signal to the brain. It is modulated by chemical mediators both at the site of injury and in the brain. Additionally it can be dampened by higher order nueronal input and the limbic system and cortex are involved in parsing the experience. That’s why essentially the exact same injury in a different context can lead to wildly different perceptions of the amount of pain. Children are an excellent example of this. I’ve watched my nephew get smacked by another kid and knocked down – he wailed and cried crocodile tears. In another instance he was running around, hit a wall because he wasn’t looking, and was knocked back – objectively a much harder hit than the smack. Yet he got right back up an kept going, no tears. When I asked him in both instances if it hurt, he said yes, but the latter case he said it barely hurt at all.

    What I am getting at is that the common physiology, if there is one, in placebo effect is of purely internal CNS involvement – reward centers, emotional response, higher order dampening, endorphin/enkaphalin release, etc. For things like pain, for which the perception and experience are extremely complex and modulation by the interaction of so many brain centers, the placebo effect can have profound effects. But when you are looking at actual wound or lesion healing, I do not think there is any such pathway that is “activated” by placebo.

    I agree with you that in cases of stress/anxiety wounds will be healed more slowly. This is because of CNS/autonomic changes that inhibit healing processes to divert resources away from healing. But I infer that the effect of placebo here is to simply change that CNS/autonomic balance and allow healing to take place normally – not to actually activate (or enhance) some sort of healing physiology. In other words, it takes away the anxiety restoring normal physiological processes. The test here would be objective measures of physical healing processes induced by any sort of placebo – and I have yet to see any.

    I also included intent in my definition for a good reason. For example, antihypertensives are also transient – remove them and the HTN comes back. Placebo can act to reduce HTN as well and is also transient. Both have objective measures. The only two differences are we know the molecular basis for anti-HTN drugs we use but the placebo is more complicated and we don’t know the precise pathway (though I would reckon it has to do with decreased sympathetic tone) and that you must tell (or at least imply to) the patient the placebo will work but you need not do so for a beta-blocker (hence the “intent” and why I consider it unethical to use placebo as treatment, regardless of the fact that it actually elicits physiology changes and sometimes objective changes as well).

  82. daedalus2u says:

    I completely agree “that the effect of placebo here is to simply change that CNS/autonomic balance and allow healing to take place normally – not to actually activate (or enhance) some sort of healing physiology.”

    But whether that improved balance actually enhances healing depends on what the basal level of those things are. If the basal level of those things is out-of-whack, then a placebo has the opportunity to restore a more appropriate balance and improve healing.

    It is like anything that you need, if you are chronically sleep deprived, then some extra sleep will improve things. If you are well rested it won’t. If you have a chronic deficiency of vitamin xyz, then a supplement will improve things. If you don’t have a deficiency, then it won’t.

    But if people are going to CAM and getting what they feel are improvements from the placebo effect, that implies to me that they are deficient in what ever it is that the placebo effect provides.

  83. daedalus2u says:

    Look at the oxytocin nestlet paper I linked to. There was a treatment (giving the rodents nestlets to build nests out of) that improved healing. Is that a placebo?

  84. pmoran says:

    To me, lumping together mistakes and artifacts of perception in with the physiology of the placebo effect is unfortunate because it adds a lot of noise to what I am trying to study.

    I am sure it does. Yet the assumption that placebo responses generally involve any single peripheral (non-CNS) physiological process or pathway is precisely what we are challenging.

    Apart from plausible psychological mechanisms for mediation of the placebo, there are even better substantiated physiological explanations than yours, ones that do not involve any excursion outside of the CNS, for example endorphin release, and the activation of what are thought to be pain relieving pathways on PET scans of the brain.

    It is not that descending neurological pathways and changes in pituitary hormone activity may not have additional, probably minor and largely unnoticeable physiological effects, depending on context and on how powerful the soothing influences are, but you are going far beyond that, and not because any firm, relevant evidence pushing you in that direction, such as that NO release is actually triggered by placebo in any target organ or tissue.

    Another problem with your theory is the woolliness (to put it mildly) of the supposed placebo-responsive pathology. You talk of “healing” and insist that you are using the usual scientific meaning of that term, whereas in most instances where placebos are “active” there is no conceivable acute tissue injury to heal. Think of sea sickness, Parkinson’s disease, depression.

    And the evolutionary approach favors the perceptual theory. Healing is a slow process. You want that fellow out hunting right now.

  85. daedalus2u says:

    PM, how does the CNS couple to the individual cells that have to do the healing? Each cell is not individually controlled by the CNS. Each cell needs to regulate its own energy status independently, and NO is what does that. What keeps the cells of a tissue compartment “in sync”? It isn’t connection to the CNS because organs can be transplanted. Why would we expect different global and local signals to regulate energy status in cells?

    There are volume neurotransmitters. A very important volume neurotransmitter is NO. NO is known to be reduced in fight-or-flight and in many other stress situations. Too little NO is known to reduce the rate of wound healing (as does too much).

    Placebos (pharmacologically inert materials said to reduce nausea) exacerbate visually induced nausea while nocebos (the same inert material said to make nausea worse) make nausea better.

    http://www.ncbi.nlm.nih.gov/pubmed/16738082

    There are other pathways that NO couples to. NO regulates the ATP concentration and the ATP level is chronically reduced in Parkinson’s and in depression. NO is what triggers mitochondria biogenesis and insufficient mitochondria is characteristic of Parkinson’s. In Parkinson’s there is chronic and ongoing loss of nerve cells in the Substantia nigra. How is that not tissue injury?

    All the neurodegenerative diseases are characterized by reduced energy status in the brain. Lowering ATP by lowering NO is one of the main pathways in the fight-or-fight response. NO has to be lowered to maximize aerobic ATP production by mitochondria, low ATP maximizes ATP production by mitochondria and (my hypothesis) turns off non-essential pathways. Muscle can work itself to death from ATP depletion, a “feature” to maximize ability to escape from bears. If muscle can work itself to death, why can’t neurons? It turns out they can, excitotoxicity is one of the main cause of death in neurons.

    PD is characterized by Lewy bodies which contain nitrated proteins. Nitration of proteins comes from peroxynitrite produced by near equimolar levels of superoxide and NO. Nitrated proteins are a sign of too little NO.

    Then there is this report showing reductions in loss of Substantia nigra cells from various PD analogs by NO donors (nitroglycerine is not a NO donor, but they use compounds that are).

    http://www.ncbi.nlm.nih.gov/pubmed/12076990

    I don’t completely agree with their explanation, I think a regulatory effect of higher NO on mitochondria fits their data somewhat better than OH radical trapping. OH radical is so reactive with everything that NO doesn’t have a chance to quench it before it does bad things.

    NO is also the volume neurotransmitter that mediates the vasodilatation observed in the BOLD fMRI technique. What BOLD measures is the relative magnetic susceptibility of the brain caused by differential vasodilatation (oxyhemoglobin is diamagnetic, hemoglobin is paramagnetic). The BOLD signal is very highly correlated with neuronal activation.

  86. daedalus2u says:

    There are plenty of examples of local control of physiology mediated through oxidative stress (which is also equivalent to low NO because superoxide destroys NO at diffusion limited kinetics). Ischemic preconditioning (IP) is extremely well documented and can be triggered solely by oxidative stress. Ischemic preconditioning is a state that tissue compartments enter after being exposed to brief periods of ischemia. It lasts for a significant period of time (a day or so), and is substantially protective against ischemic insults during that period.

    In other words, brief periods of ischemia trigger ischemic preconditioning which is protective against longer ischemic events. IP is characterized by a lower ATP concentration, a lower ATP production rate, and a lower ATP consumption rate. IP has been documented to occur in multiple tissue compartments, heart, brain, liver.

    Can IP be a state that tissue compartments or organisms can stay in long term? No, it can’t. If IP was consistent with long term survival and reproduction, then organisms would have evolved to be in that state permanently and reduce basal ATP consumption to have more ATP available for reproduction. Organisms have not done that, so there must be something about IP that is incompatible with long term health, life, or reproduction.

    If ATP consumption is reduced, it must be that some pathways are turned off. It can’t be that pathways are simply reconfigured to be more efficient, because if organisms could do that, they would have evolved to be in that state permanently so as to have more ATP for reproduction.

    How many ATP consuming pathways are involved? It can’t be just a few because turning off just a few would not supply enough ATP to account for the reduced consumption. It must be many pathways. Each cell in a tissue compartment exhibiting IP reduces its ATP consumption. Because these are different cells doing different things, presumably different ATP consuming pathways are turned off in different cells. If many different cells and different types of cells in a tissue compartment are regulated to exhibit IP simultaneously, there must be common signaling that mediates this synchronous behavior.

    Since the triggering of IP can be local (it can be triggered by artery occlusion), that triggering does not (necessarily) involve the CNS. If there is local triggering of IP in multiple cell types by a common local signal, and communication of IP triggering between local cells (necessary for whole tissue compartments to enter and leave IP “in sync”, presumably, if there is triggering of IP by the CNS, it is the activation of local IP triggering signals by the CNS that does so. (It being much easier to evolve CNS triggering mechanisms for an already existing local pathway than to evolve redundant and independent de novo pathways.)

    Since IP is triggered by local oxidative stress, if there was a CNS mechanism to trigger local oxidative stress, that signal could be used to trigger local IP. It turns out there are CNS mechanisms to trigger local oxidative stress.

    The archetypal pathway to control blood flow is vascular tone. The heart generates a pressure gradient between its inlet and outlet and the flow of blood through the vasculature is determined by the pressure drop across the vasculature which is controlled by the relative cross sectional area of different parts of the vasculature. Because the volumetric output of the heart is limited, blood flow is directed to a particular tissue compartment by increasing the cross section of vessels serving that tissue compartment and simultaneously decreasing the cross section of vessels serving tissue compartments receiving less blood. Physiology has to do both simultaneously; it must dilate vessels to deliver more blood to some tissue compartments while constricting vessels to deliver less blood to other tissue compartments such that the output of the heart remains at what it is controlled to be maintained at.

    It turns out that the archetypal regulator of vascular tone is NO. More NO dilates vessels and less NO constricts them. There is local control of NO generation via shear at the endothelium. Generation of NO causes vasodilatation, generation of superoxide causes vasoconstriction. There is neurogenic production of NO and of superoxide.

    Since physiology does have a mechanism to reduce NO levels in each tissue compartment that has blood flow regulation (that would be all tissue compartments), that same NO changing pathways could be used to trigger or anti-trigger ischemic preconditioning.

  87. daedalus2u says:

    What happens if IP is triggered and then maintained indefinitely? I have established that IP can’t be a permanent state or organisms would have evolved to be in it indefinitely. Eventually bad stuff must happen that compromises the function of that tissue compartment. We know that muscle can be worked to death under conditions of ischemia. That is why infarcted hearts develop infarcts. But a non-beating heart can be kept ischemic a long time without damage (as in during transport of explanted hearts).

    If a beating heart can beat itself to death, then presumably consumption of ATP to continue beating is one of the last ATP consuming pathway to stop consuming ATP. Because there is a loss of viability, the pathways that consume ATP to maintain viability have been turned off earlier, presumably to supply ATP to continue beating. We know this because if the heart was not beating (as in the explant), then viability is maintained for much longer.

    In any viability hierarchy, repairing damage (i.e. healing) must have a lower priority than maintaining viability (staying alive) because maintaining viability is equivalent to repairing damage that would be fatal in the very short term.

    What long term effects should we see if IP goes on for too long? First, how long can IP go on for? Presumably it can persist until the tissue compartment dies. How long that takes will depend on the degree of IP, and the metabolic load during IP and how much and what sorts of compensatory tissue remodeling go on during the long term IP.

    IP is characterized by oxidative stress. Oxidative stress is characterized by and is identical with a state of low NO. A state of IP is a state of low ATP, high superoxide and low NO. Low NO will lead to low blood flow and low substrate delivery. How do tissue compartments cope with low substrate delivery? The premise of this thought experiment is that the state of IP continues long term. The continuation of IP long term is not compatible with increased consumption of substrates in a tissue compartment. IP is a state of reduced substrate consumption of substrate by a tissue compartment. Long term consumption by cells of substrate at the substrate consumption rate characteristic of IP is not compatible with long term survival of those cells. If the substrate consumption of the tissue compartment cannot increase, then the substrate consumption of individual cells in that tissue compartment can increase only if some of the cells die. At some point the only way that some cells in the IP impacted tissue compartment receive sufficient substrate to survive is by some cells being ablated.

    If less substrate is being delivered, the vasculature will remodel to reflect reduced substrate delivery, that is there will be capillary rarefaction.

    Functionality of the tissue compartment will decline because insufficient substrate is delivered to the tissue compartment to maintain function and viability. This functional decline may be slow to observe at first because there is redundancy. That redundancy is the first thing to go, after it is gone, then needed functionality declines. The tissue compartment will remodel to try and preserve function but that remodeling will be ineffective because there is insufficient substrate delivery. For example the heart muscle will get weak because of insufficient substrate to maintain strength, but the heart will get bigger to try and compensate as in dilative cardiomyopathy.

    Decline will be observed first in the longest time constant pathways, the pathways that can be put off for the longest time. For example, axonal transport takes a long time (days to weeks), that can easily be put off for a few hours to days. Mitochondria turnover is slow, (weeks to months), that can be put off for days to weeks. Autophagy can be put off. Autophagy consumes ATP and only provides substrates. In an ATP crisis (as IP is), it is better to put off autophagy until later. The damaged proteins that accumulate are not too much of a problem at first, if they generate a little bit of ROS, so much the better at maintaining the hysteresis of the IP state with less energy input.

    DNA repair can’t have as high a priority as using ATP to maintain cell viability. We should see an accumulation of DNA defects.

    In summary, what should we expect to see if IP goes on for too long?

    Reduced ATP production,
    Reduced substrate consumption.
    Reduced blood flow
    Capillary rarefaction
    Oxidative stress
    Accumulation of damaged mitochondria
    Accumulation of damaged protein inclusions
    Reduced intracellular transport in axons (i.e. reduced water diffusivity)
    Reduced functionality of tissue compartment
    Accumulation of metabolically inert fibrous tissue
    Accumulation of DNA defects.
    Apoptosis of cells

    How many of these symptoms do we observe in the various degenerative diseases of the high metabolic tissue compartments? Brain, heart, liver, kidney? As far as I can tell from the literature, all of them.

  88. I’m curious how current the information in the paper is. I notice that it is from 2000. In 2003 and 2005 our family hospital implemented a policy that banned gifts, “souvenirs”, food, drink, etc to clinicians as well as other policies that are modeled after the AMA opinions on ethics and drug companies representation.

    It seems to me that I have heard of other hospitals in the area taking up similar policies.

    It seems stuffed animals with medication emblems may be becoming a thing of the past.

  89. whoops, that was supposed to be posted in another thread. Sorry.

  90. Ali771 says:

    @ Scotton (22 Jun)
    “Typically the woomeisters claim that there is no tradeoff. Not only will their magic diet make you live forever, it’s also the tastiest and easiest to prepare food ever! And it’ll make you the greatest genius in history! And prevent global warming! And eliminate dependence on foreign oil! And ensure 0% unemployment and 20% annual GDP growth!”

    Love it.
    That’s because they’re preaching a religion and feeling right feels soooo good!

  91. Ali771 says:

    @ Scott (22 Jun)
    “Typically the woomeisters claim that there is no tradeoff. Not only will their magic diet make you live forever, it’s also the tastiest and easiest to prepare food ever! And it’ll make you the greatest genius in history! And prevent global warming! And eliminate dependence on foreign oil! And ensure 0% unemployment and 20% annual GDP growth!”

    Love it.
    That’s because they’re preaching a religion and feeling right feels soooo good!

  92. pmoran says:

    D2:PM, how does the CNS couple to the individual cells that have to do the healing? Each cell is not individually controlled by the CNS. Each cell needs to regulate its own energy status independently, and NO is what does that. What keeps the cells of a tissue compartment “in sync”? It isn’t connection to the CNS because organs can be transplanted. Why would we expect different global and local signals to regulate energy status in cells?
    ———————————————————–
    The problem remains that there is no evidence to connect any of this to placebo influences. .

    Specifically, there is no evidence that within archetypal placebo responses such as pain relief anything at all is occurring at the level of the cells of peripheral (non-CNS) tissues, nor that it has anything to do with any commonly accepted understanding of the word healing. I would advise against using that word. If you truly mean the stimulation of repair processes within damaged tissue say so and be prepared to describe that damage if you can.

    Placebo responses are so far separated from the low-level, mostly almost wholly automated physiological processes that you wish to recruit into the placebo discussion that in most settings is it very difficult or impossible to distinguish it from biassed reporting i.e. patients supplying the answers they think are expected.

    That is an Achilles heel to the whole placebo issue and it applies to your field as much as the debate I have been trying to get a resolution to, because I think it is so vital to how we react to some elements of CAM.

    I won’t comment further unless I think I have found a better way of conveying why your views are so difficult to accept, for those of us on the more clinical side of medicine.

  93. daedalus2u says:

    PM, what basis do you have for stating that

    “Placebo responses are so far separated from the low-level, mostly almost wholly automated physiological processes that you wish to recruit into the placebo discussion that in most settings is it very difficult or impossible to distinguish it from biassed reporting i.e. patients supplying the answers they think are expected.”

    I agree that in most settings it is difficult or impossible to distinguish it from biased reporting. That is always true of all discussions of all things. Biased reporting can mimic any effect that can be reported. You are asserting that there is no connection in the absence of evidence, I am asserting that there must be a connection because “ the low-level, mostly almost wholly automated physiological processes” are activated by the placebo effect in some circumstances, so the placebo effect must have the ability to recruit those physiological processes.

    I am not saying that all placebos always activate all of these low-level processes, but if any low-level processes are activated by placebos (which they are), then placebos are activating them. I am not saying that we know the mechanism, I very strongly hypothesize that NO physiology is highly involved for a variety of reasons based on very credible data in the literature.

    There is great variation in the quality of the research on placebos in the literature. One has to read it very carefully to avoid bias in both directions, the bias of researchers wanting to see effects that are not there and researchers wanting to not see effects that are there. You have to look at all the literature and give each piece of it appropriate weight.

    Placebo surgical treatments for angina work better than doing nothing. They also work better than ligation of the internal mammary artery. The scientific American article by Walter A Brown “The Placebo Effect” has some nice charts showing this. Any explanation of the placebo effect has to be consistent with this data. An explanation limited to perceptional error is not consistent with this data. I have to reject the perceptional error hypothesis of all aspects of the placebo effect.

  94. nybgrus says:

    @daedalus:

    I did a very brief search, so not even remotely complete and would thus welcome any citation to the contrary but…

    is there any study showing that the placebo effect can change objective outcomes? I am quite aware that angina responds well to placebo (heck, it was even written about in the NEJM in 1979) but do outcomes actually change? Do people have decreased mortality as result?

    I do know of a study (can’t find the link ATM but Gorski wrote about it sometime back) that shows people with osteoarthritis respond well to placebo claiming subjective improvements with pain and even mobility, but when comparing onjective measures there was no difference despite the reporting.

    This article from Brain: A Journal of Neurology is a meta-analysis of placebo effects (from 2008) and discusses the various neurotransmitter effects of placebo, and heavily focuses on the interesting pain studies in which nalaxone can block placebo induced analgesia. There were a few references to objective changes, but I feel like I have to nitpick at them. All were in systems that were dynamic and under control of the CNS and/or various neurotransmitters – which can easily be explained by differential CNS/autonomic activation. The only one that stood out to me was an objective rise in LFTs (specifically ALT) through placebo. So I checked out the article the referenced this(Fulltext PDF). It was a meta analysis, but at the end only had n=100 and of those only 22 were found to have increased LFTs. This was significant, and they determined that a sensitivity of specificity of roughly 75% could be assigned to predicting raised ALT via placebo. In the discussion they discuss a number of limitations and confounding factors which could have influenced the data. Additionally, from my own experience LFTs can fluctuate quite a bit in your average person regardless of intervention, so I am not too sure about these results really meaning anything, but I’ll admit it does sound interesting to me.

    However, in light of everything else demonstrating only effects that are subjective or objective but directly modulated through autonomic nervous systems, I’m still unconvinced that there are any truly objective effects of placebo. Your common pathway for healing would, to me, simply be the existing background healing activity that is omnipresent in the body. During times of stress, I absolutely agree that would be depressed and resources spent elsewhere. Placebo can “trick” the body into thinking it is OK to not be stressed and thus restore healing processes to full capacity – but I do not think that any placebo could independently and directly activate or enhance such a healing process. In other words, if a person is already non-stressed and healing at maximum capacity, placebo will do nothing to objectively change that.

  95. daedalus2u says:

    I think I agree with you, that if a person’s healing capacity is already at the nominal optimum that placebos will have no effect.

    I don’t think that placebos per se will increase ALT or other LFT. The stress of being in a trial might, or some random exposure to some unknown infection might. The change in LFT associated with being on placebo may have been a post hoc ergo prompter hoc.

    What evidence do we have that for most people seeking medical care that their healing capacity is already at the nominal optimum? It is my understanding that most people who seek medical care do so because they perceive sub-optimal health characteristics. If people are helped by placebos (i.e. virtually all CAM treatments), even if only subjectively, doesn’t that imply that the placebo is supplying something that the individual was deficient in?

    I think there is a great deal of fluctuation in healing capacity that is not noticed because the time constants of healing are long compared to the fluctuations. There is no instrumental way to measure “healing capacity”, so we have no way of knowing what it is moment to moment. Presumably it can change as rapidly as the systems mobilized by stress can change. If systems to cope with stress can be turned on in a few minutes, the systems that need to be turned off to supply the resources the stress response systems need must be capable of being turned off just as fast.

    In any case signaling is used to regulate healing up and down during non-stress and stress states. If that signaling is interfered with, then the regulation of healing up and down will be not as precise. This will most likely result in slowed healing because healing does not have the highest priority (or stress would not slow it down).

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