Reiki (pronounced raykey) is a form of “energy healing,” essentially the Asian version of faith healing or laying on of hands. Practitioners believe they are transferring life energy to the patient, increasing their well-being. The practice is popular among nurses, and in fact is practiced by nurses at my own institution (Yale).

From reiki.org, we get this description:

Reiki is a Japanese technique for stress reduction and relaxation that also promotes healing. It is administered by “laying on hands” and is based on the idea that an unseen “life force energy” flows through us and is what causes us to be alive. If one’s “life force energy” is low, then we are more likely to get sick or feel stress, and if it is high, we are more capable of being happy and healthy.

Reiki is therefore a form of vitalism – the pre-scientific belief that some spiritual energy animates the living, and is what separates living things from non-living things. The notion of vitalism was always an intellectual place-holder, responsible for whatever aspects of biology were not currently understood. But as science progressed, eventually we figured out all of the basic functions of life and there was simply nothing left for the vital force to do. It therefore faded from scientific thinking. We can add to that the fact that no one has been able to provide positive evidence for the existence of a vital force – it remains entirely unknown to science.

But the discarded science and superstition of the past is the “alternative medicine” of today. There are many so-called “CAM” modalities that are based on vitalism, including Reiki. Reiki, in fact, is very similar to therapeutic touch, another energy healing modality that was popular among nurses, and although it continues to be used it is much less popular after 9 year old girl (Emily Rosa) performed an elegant experiment to show that it was nothing but self-deception. Reiki nicely moved in to fill the void.

The research on Reiki, and energy healing in general, is similar to that of many similar modalities – those with very low scientific plausibility that are not taken very seriously by medical scientists. The research is of generally low quality, poorly controlled small studies that seem designed to justify Reiki rather than see if it actually works. The most recently published study, for example, looks at anxiety levels and self-reported well being in cancer patient and finds, unsurprisingly, that patients feel better when they receive the kind attention of a nurse. The study is completely uncontrolled, and therefore of dubious value. One might consider such a study a complete waste of time and effort, as the results were never in doubt.

A 2011 review of reiki studies concluded:

The existing research does not allow conclusions regarding the efficacy or effectiveness of energy healing. Future studies should adhere to existing standards of research on the efficacy and effectiveness of a treatment, and given the complex character of potential outcomes, cross-disciplinary methodologies may be relevant. To extend the scope of clinical trials, psychosocial processes should be taken into account and explored, rather than dismissed as placebo.

In other words – existing research is a such poor quality we cannot draw any useful conclusion from it. I disagree, however, that this necessarily means that more research is needed. The low plausibility of using magical energy that has never been demonstrated to exist by medical science argues otherwise. Further, the last sentence is odd – it suggests the authors are trying to spin placebo effects into real effects. This is increasingly the strategy of alternative medicine advocates as it becomes clear that most of the modalities they favor do not work any better than placebo (which means they don’t work).

Reiki is now squarely in that camp. Published at about the same time as the review (and therefore not included in the review) is a well-designed study of Reiki where Reiki was compared to placebo Reiki (someone not trained in Reiki simply goes through the motions) vs usual care (no intervention). Not surprisingly, both the real Reiki and the sham Reiki groups did better on self-reported well-being than the no intervention group, but they were indistinguishable from each other. Therefore Reiki did not better than placebo. That means Reiki doesn’t work (at least in the regular world of science-based medicine).

The authors conclude:

The findings indicate that the presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels, with or without an attempted healing energy field.

I notice the authors did not conclude “Reiki doesn’t work.” This is odd, given that both the treatment and placebo groups had the same effect on subjective outcomes. With regular medical interventions we conclude from this outcome that the treatment does not work. Imagine a pharmaceutical company concluding:

The findings indicate that taking a pill during chemotherapy was influential in raising comfort and well-being levels, with or without an active ingredient.

Therefore – taking pills is helpful. Let’s not fret about whether the active ingredient has any specific physiological effects. Reiki supporters appear to have taken a page out of the acupuncture handbook. If real and sham acupuncture are both better than no intervention (they argue), than acupuncture works, whether real or placebo.

This article by Edzard Ernst recently published in the Guardian also discusses this Reiki study. Ernst points out that, not only is it scientifically dubious to conclude from such studies anything other than the treatment does not work, it is ethically questionable to give such treatments as a placebo intervention. He writes

By insisting that patients must not be treated with placebos like reiki, scientists also advocate that they receive treatments that demonstrably work better that placebo. For instance, massage has been shown to improve the wellbeing of cancer patients beyond a placebo effect. If a patient receives a massage with empathy, sympathy, time, understanding and dedication, she would benefit from the placebo effect – just like the reiki patient – but, in addition, she would also benefit from the specific effect of the treatment that massage does and Reiki does not offer.

This is a critical point that I have been making also. Essentially, you cannot justify ineffective treatments simply because they provide a placebo effect. That is because effective treatments also provide the same placebo effect, but also provide specific benefits because they actually work.

I would argue that there are also many potential harms from convincing patients that unscientific treatments are effective because of their non-specific placebo effects. This is a deception, violates patient autonomy and informed consent, and sets them up to perhaps rely on ineffective “magical” treatments for non-self-limiting illnesses.

Let’s get back to the authors conclusions from the Reiki study – they argue that this study shows that the:

“presence of an RN providing one-on-one support during chemotherapy was influential in raising comfort and well-being levels…”

The part about “with or without an attempted healing energy field” is entirely irrelevant, and you could just as well substitute any ineffective or magical treatment for “healing energy” is that statement. But the first part of the conclusion is also dubious, in that we did not need this study to come to this conclusion.

It has already been well-established, to the point that it is appropriately taken as a given, that people feel better when they get the kind attention of someone else, especially if they are sick and that person is a health care professional with training and experience in comforting sick patients. We don’t need to keep studying this over and over again.

Kind attention plus X makes people feel better, just as well as kind attention alone. Great. We do not need to study this with every possible form of unscientific intervention filling in for X. And it is deceptive and unscientific to suggest that whatever fills in for X has some value because of this equation.

This is what I call the “part of this complete breakfast” fallacy. Even as a child I recognized that when a commercial advertised their pastries as being part of the complete nutrition offered by an otherwise nutritious breakfast, the pastries were nutritionally irrelevant. They added nothing, and the commercial was being deceptive in trying to make me think that they were nutritious simply by their proximity to a nutritious breakfast.

Reiki, acupuncture, homeopathy, and similar methods may be “part of this feel-good intervention,” but they are an irrelevant and superfluous part. It is the kind attention of the practitioner that matters – and only that attention. So such attention might as well be part of legitimate science-based interventions that also have a specific physiological benefit.

This suggests that the real purpose of the ritual of reiki, or other superfluous placebo ritual, is not to achieve a positive end for the patient but to give the practitioner a marketable “skill” (even though the evidence shows that someone without any such skill or training can get the same results). In a recent article about reiki making its way into hospitals, Kryak and Vitale write:

There is a growing interest among health care providers, especially professional nurses to promote caring-healing approaches in patient care and self-care. Health care environments are places of human caring and holistic nurses are helping to lead the way that contemporary health care institutions must become holistic places of healing. The practice of Reiki as well as other practices can assist in the creation of this transformative process.

I submit that if the goal is to make hospitals and other health care environments more nurturing, promoting reiki and similar modalities is that exactly wrong way to do it. They are tying a worthwhile goal to blatant pseudoscience, and therefore legitimate resistance to the pseudoscience will also cause resistance to the nurturing.

If we accept that health care environments can be improved by more time and resources being applied to patient comfort, reduced anxiety, and enhanced self sense of well-being – then let’s use what works, the time and attention of a caring provider. The placebo ritual that is reiki (or acupuncture, or whatever) is wasteful, distracting, and arguably unethical. It unnecessarily complicates efforts to improve patient caring by promoting demonstrable pseudoscience.

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From a message posted on Facebook:

 Is the pill safe? The International Agency for Research on Cancer in a 2007 study made by 21 scientists reported that the pill causes cancer, giving it the highest level of carcinogenicity, the same as cigarettes and asbestos. It also causes stroke, and significantly increases the risk of heart attacks. Several scientific journals have stated that the natural way of regulating births through the Billings Ovulation Method has no side-effects, and is 99.5 % effective.

The Billings Ovulation Method (BOM) is a method of natural family planning where women are taught to recognize when they have ovulated by examining their cervical mucus, allowing them to avoid intercourse during fertile periods or conversely, to have intercourse during fertile periods when pregnancy is desired. We used to call people who used the rhythm method “parents,” but BOM is more reliable than older abstinence methods.

I’m a big fan of oral contraceptives. They contributed to women’s liberation by giving us a reliable method of planning, delaying, or avoiding pregnancy.  They also have medical uses that go beyond contraception. Birth control pills (BCPs) have had such an important impact that they are known as simply “The Pill.” We have always known they were not 100% risk free; but we also know they are less risky than pregnancy itself. There are other methods of birth control; but they are generally less effective and less convenient.  For those who want permanent solutions, tubal ligation and vasectomy are available; but even they have occasional failures. What does science tell us about the effectiveness and safety of BCPs as compared to other methods? 

Effectiveness 

According to the Wikipedia entry, the Billings Ovulation Method has a failure rate of 0-2.9% with perfect use and 1-5% with typical use.  (They cite the original references for these figures). The corresponding numbers Wikipedia gives for “the pill” are 0.3% and 8%. The American Congress of Obstetricians and Gynecologists’ numbers for the pill are a bit less optimistic: they say “With typical use, about 8 in 100 women (8%) will become pregnant during the first year of using this method. When used perfectly, 1 in 100 women will become pregnant during the first year.”

A handy table on the FamilyDoctor website compares the failure rates of various birth control methods. It lists periodic abstinence methods as having a 20% failure rate, but that includes the less effective rhythm methods as well as the methods based on mucus examination. 

Cancer? It Causes Some Cancers and Prevents Others 

Information on cancer and oral contraceptives can be found here.  There is an increased risk of cervical cancer, but most cases are related to HPV infection, so hopefully the new vaccines will eliminate much of that risk. There is an increased risk of liver cancer in low risk populations but not in high-risk populations. The risk of breast cancer may or may not be slightly increased: studies do not agree.

On the other hand, the pill clearly reduces the risk of uterine and ovarian cancers. And a meta-analysis found that the risk of colorectal cancer is also decreased.

The magnitude of these risks is small. I couldn’t find any information about overall cancer risk: whether the increase in some types of cancer outweighs the decrease in others.

What the IARC Really Said 

According to the Facebook poster, the International Agency for Research on Cancer (IARC) said oral contraceptives were as carcinogenic as cigarettes and asbestos.  That’s not what the IARC said at all. It does classify estrogen/progesterone in the same group 1 category as cigarettes and asbestos, but all that category means is that there is sufficient evidence to prove carcinogenicity in humans. It does not in any way imply that oral contraceptives are as carcinogenic as cigarettes and asbestos: they aren’t.  And the IARC entry clearly states

There is also convincing evidence in humans that these agents confer a protective effect against cancer in the endometrium and ovary.

Other Risks

BCPs increase the risk of deep venous thromboembolism and ischemic stroke. There is disagreement over whether they increase the risk of myocardial infarction. The absolute risk of all these conditions is low. It is greater in smokers and in those with other risk factors, and it is lower for the newer low dose BCPs.

The ACOG has prepared an excellent patient education pamphlet  listing all the risks, benefits, side effects, and contraindications.  It concludes:

 The pill is a good choice for women who may want to get pregnant later. It is a safe and effective way to prevent pregnancy. It is easy to use, convenient, and reversible. The pill may protect against some cancers. Some benefits of pill use last months or years after you stop taking it. For almost all women, the benefits of pill use outweigh the risks.

Benefits

Critics of hormonal contraception fixate on the risks, but there are also a number of health benefits. The ACOG patient information pamphlet explains that BCPs reduce the risk of

• Cancer of the uterus and ovary
• Ovarian cysts
• Pelvic infection
• Bone loss
• Benign breast disease
• Symptoms of polycystic ovary syndrome
• Anemia (iron poor blood)
• Ectopic pregnancy
• Acne

They also

• Help to keep periods regular, lighter, and shorter and reduce menstrual cramps
• Reduce symptoms of endometriosis and fibroids
• May help with migraine headaches and depression.
• Can be used to schedule periods to avoid an inconvenient time (i.e. a wedding).

Other Options

There are many other birth control options: condoms, diaphragms, other hormone delivery methods like cervical rings and injections, IUDs, spermicides, periodic abstinence methods, and therapeutic abortions. Some methods have the additional benefit of protection against sexually transmitted diseases. Some methods require specific actions at the time of intercourse, which some people object to as interfering with spontaneity. The periodic abstinence methods have the disadvantage of requiring periodic abstinence.

I remember reading years ago (the reference is long gone and I don’t know if the information is still valid) that when all factors were considered including the risks from pregnancy itself when contraception fails, the safest method of birth control was to use condoms and do therapeutic abortions when they failed. That resulted in statistically less morbidity and mortality overall than any other method. Of course there are other considerations that make this a less than ideal option. Emotions and religion create a lot of bias in the area of birth control. I suspect some people who reject oral contraceptives as “unsafe” might be quite willing to take other medications that have a similar safety profile but are not connected to ideological concerns. 

Conclusion

BCPs are not risk-free, but the Facebook poster was wrong: their risks can’t be compared to the risks from cigarettes and asbestos. There are other good alternatives that some individuals may prefer for various medical and non-medical reasons. For any method of birth control, the risks must be weighed against the benefits. Pregnancy itself is far riskier than any method of pregnancy prevention.

The safest, most effective method of birth control is orange juice. You may ask “Before or after?” The answer is “Instead of.” Most women and their partners would not consider that a satisfactory option.

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Editor’s note: Having just submitted a major grant on Friday and then having had to turn around and head to an NIH study section meeting today in Bethesda, I just didn’t have the time to produce something up to the usual standards of SBM for today. (And, being managing editor, I should know what’s up to the usual standards of SBM; what I started to write wasn’t it. Trust me on this.) Fortunately, Dr. Grant Ritchey and Dr. Steve Hendry, two skeptical, science-based dentists, did submit something up to SBM’s usual standards. Even better, since we’ve been having a number of requests for posts involving dentistry, it seemed like a perfect time to publish their first contribution to SBM and see how our readers like it. Maybe next time around, I’ll have them update the “state of knowledge” regarding amalgams.

Form follows function, as the old saying goes. Nowhere in the human body is this adage more fitting than in the oral cavity.  In less than two generations, the practice of dentistry has evolved from basic pain relief and function-based procedures (such as extractions and fillings), into today’s practices of complex cosmetic rehabilitation, orthopedic and orthodontic management of the teeth, jaws, and facial structures, replacing missing teeth with dental implants, and treatment of sleep apnea and temporomandibular joint (TMJ) disorders, to name but a few.   With such rapid progress, it is to be expected that for every science based advance made in our field, there are just as many claims that are either dubious in their evidential support or outright pseudo-scientific or anti-scientific nonsense.

In this article, we’ll be taking a look at the roles that health care practitioners such as chiropractors, osteopathic physicians, and physical therapists, are attempting to play in the dental field.  We will also see how well-meaning dentists have been trained in and apply their pseudo-scientific principles in their dental practices. In particular, we’ll be examining Cranial Osteopathy (also known as Craniosacral Therapy or Cranial Therapy) in the management of the dental patient, the purported benefits claimed by practitioners of cranial osteopathy, and the quality and quantity of evidence for this type of treatment in the scientific literature.

Basic Skull Anatomy

The human skull is made up of some eight cranial (head) bones and fourteen facial bones.  These bones help protect the organs of vision, hearing, taste, equilibrium, and smell. They also provide attachment for muscles that move the head, control facial expressions and chew our food.  At birth, the spaces between the cranial bones- called fontanelles – are wider and more elastic, allowing the infant to pass through the birth canal and later permitting brain growth in the first few years of life.  In humans the lateral fontanelles close soon after birth, the posterior fontanelle generally closes several months later, and the anterior fontanelle may remain open for three years.

By early childhood, the cranial bones become tightly interlocked in a zig-zag, zipper like pattern (illustrated nicely here) that renders them immovable in a macroscopic sense, although each suture (called a synarthrosis if you want to impress your friends at parties) has a very slight amount of flexibility- 10-30 micrometers on average (1 micrometer = 1/1000th of a millimeter or approximately 4/100,000ths of an inch).  These sutures fill the minuscule space between the cranial bones, essentially stitching them together with dense, strong connective tissue fibers called Sharpey’s fibers.

Tenets and Scope of Cranial Osteopathy

Cranial Osteopathy was invented by William G. Sutherland D.O. around 1900 when, while viewing a disarticulated human skull, he noted the way some of the skull bones were:  “…beveled… like the gills of a fish… indicating articular mobility… for a respiratory mechanism.”   Note that we said “invented” rather than “discovered,” as this discipline was indeed invented from whole cloth, based upon the happenstance similarity in the appearance of a skull bone and the gills of a fish, which he then superimposed on his 19th century osteopathic ideology.  (Imagine what he would have come up with had he instead noted the similarity between the uvula and the male genitalia!)  Sutherland claimed, and adherents of Cranial Osteopathy hold, that the cerebrospinal fluid (CSF) has an inherent rhythmicity, which he likened to the tides of the ocean.  He called this the “Primary Respiratory Mechanism (PRM)”, often referred to today as “Craniosacral Rhythms.”  According to Osteopathic principles, the PRM underlies all of life’s processes and begets vitality, form, and substance to all of a person’s anatomy and physiological processes.  Any disturbance in the natural flow of CSF could cause illness and conversely, practically any illness could be prevented or cured by the physical manipulation of the cranial bones, “freeing up” the functional flow of the CSF.   Towards the latter part of his life, Sutherland believed that he could sense a “power” which allowed corrections to occur from inside his patients’ bodies without having to provide any physical manipulations.  This has come to be known as “biodynamic craniosacral therapy” or “biodynamic osteopathy”.  See this overview of the scope of Cranial Osteopathy (“The Cranial Concept”) in their own words.

Of course, none of this imagery would be of any use without a therapy to sell, and osteopaths assert that they can fix what ails you through hands-on manipulation of your skull bones. As one practitioner’s website puts it:  “As incredible as this may seem, we feel the bones move, the membranes pull, the fluids fluctuate, and even the brain undulate”.  And woe unto the poor sap who suffers from a rigid-boned, lax-membraned, fluid stasisy, un-undulating brain!  Practitioners of Craniosacral Therapy or Cranial Osteopathy claim that they can detect this secondary CSF pulse with simple palpation and distinguish them from a regular vascular pulse.

Cranial manipulations are performed in a variety of different ways depending upon the condition being treated and the philosophy and training of the practitioner.  (See an overview of some of the techniques.)  Some of them include range of motion therapies similar to what a physical therapist would do; others involve the supposed manipulation and movement of the cranial bones, using only digital (i.e. finger) pressure with a very light force.

The Cranial Osteopathic Academy, a component society of The American Academy of Osteopathy (AAO), described it thus:

Treatment is typically very gentle. Tissues are supported and allowed to change. Usually very little force is used during treatment, but at times some force may be necessary. Diagnosis and Treatment are said to blend into one another. As tissues change the physician learns more about their nature. As the nature of the tissue dysfunction is better understood, the therapeutic response deepens.

Each patient’s experience is unique. Some patients sense only a gentle touch, while others feel their body change immediately. Some patients simply feel a deep sense of relaxation, and others feel nothing at all. Most patients feel a distinct change following the treatment.

Though Cranial Osteopathy is very gentle, patients can occasionally experience some discomfort during certain stages of the treatment. When this occurs, it is simply a part of the healing process. As the treatment progresses, the discomfort subsides.

Although physicians practicing Osteopathy in the Cranial Field will work anywhere on the body, they may find it important to diagnose and treat the head. Though styles of treatment may vary, the osteopathic physician will primarily focus on the body’s “mechanism” – the body’s natural striving for health and normal function.

According to Dr.Sutherland, within each patient there is great wisdom, an inner physician, a wise all-knowing force that is the source of all healing. In his own words: “Allow physiologic function to express its own unerring potency rather than apply blind force from without.”

Cranial Osteopathy and its variants make a number of imaginative leaps from histological starting points to therapeutic endpoints.  From the slight (micrometer) flexibility of cranial sutures, and the slight-but-measurable fluctuation in CSF pressures, practitioners infer that the brain and spinal cord undulate rhythmically “like a jelly fish, coiling and uncoiling” which is critical for health.

Dental Applications of Cranial Osteopathy

Gradual movement of teeth within bones, and gradual orthopedic movement of facial bones themselves, are familiar to all dentists who do orthodontics.  Dentists performing orthodontic treatment utilize various appliances to expand the palate (palatal sutures don’t normally fuse until adolescence) and move teeth within the jawbones.  Further, the treatment of TMJ disorders has typically been in the realm of the dentist, involves the articulation of cranial bones in the scope of treatment (the mandible and the temporal bone), so the Osteopathy belief system would seem a natural fit to dentistry, especially in these areas.  And sure enough, Osteopathy has colonized the dental profession. We’ve seen expensive dental continuing education courses with “Cranio-”, “Sacro Occipital Therapy” and “Chiro-” in their names that graft Osteopathic principles onto dentistry to create whole new, untapped disciplines to market.

Websites promoting these dental applications of Cranial Osteopathy claim to teach amazing new skills to dentists, including how to “free up” and move facial bones around, by hand, in minutes using only fingertip pressure.   Additionally, in almost every case, these dental courses provide a gateway to other, more garden variety forms of CAM: nutritional supplements, detox, immune system boosting,  nervous system balancing, and so forth. For the dentist, taking one of these courses is the first step in going “down a rabbit hole” into CAM-land – a metaphor that devotees enthusiastically embrace and frequently use.

An important point to reiterate here is that the emphasis in the dental application of cranial osteopathy is not merely to treat illness or facilitate the flow of the CSF as in “regular” osteopathy; it claims to actually bodily move the facial and cranial bones to more ideal positions to improve orthodontic and TMD outcomes.  Cases are shown where overall changes in facial structure and the occlusion (i.e. the bite) are alleged to have been changed by as much as a half of an inch or more by cranial manipulation alone.  Of course, these are case studies with little to no supplementary documentation (radiographs, CT scans, etc.) available for an objective reviewer to confirm the claims. We have yet to see a well-documented, objectively presented case study in the medical or dental literature which adequately demonstrates the validity of the treating practitioner’s claims, although one would think that after decades of the existence of their treatment modalities, such evidence would be plentiful, substantive, and readily accessible to the health care community.

Credibility as a Dental Treatment

For Cranial Osteopathy to be viable treatment, there needs to be good evidence anatomically and histologically that the sutures are indeed movable (by hand, no less) to a significant degree, and evidence that doing so is therapeutically beneficial.   Neither appears to exist. Although Cranial Osteopathy can provide a modicum of basic research to support its claims, it falls far short of what is needed to establish a scientific foothold in the dental-medical community. Osteopathic applications are woefully lacking in any substantive research but instead rely on anecdotal evidence as the foundation of its validity and applicability.  See the excellent overview of Cranial Therapy at Quackwatch.org.

Evaluating the literature, minute movements of the cranial bones appear to be possible (in the micrometer range as stated above) — but not the large rearrangements of bones that practitioners claim to make with hands-on manipulation.  It is dubious that a practitioner can feel distortions in cranial bones that the most sensitive neurophysiological instruments cannot.

Moreover, even if an Osteopathic therapist could detect abnormalities in the skull, there appears to be no credible evidence linking small movements at cranial sutures to beneficial health outcomes.  As a scientific principle, this is nothing more than wishful thinking and resembles faith healing more than evidence based medicine. The therapeutic claims, research protocols, treatment goals, and definitions of what constitutes solid medical evidence are as flexible as the cranial bones they purport to manipulate.

Cranial Osteopathic adherents predictably scold their critics as being closed-minded and unwilling to learn, or worse, a shill for the Dental Industrial Complex.  But we like the old adage about staying open-minded, but not so open that your brain falls out.  The really surprising (and disturbing) thing to us is the number of bright, conscientious, and highly-trained dentists we see being drawn to courses in Cranial Osteopathy, and in many cases buying into the smorgasbord of alternate-medicine courses offered as side dishes at the cranio-dental table. If there’s harm in the Cranio-dental movement, besides a lot of money wasted by dentists on dubious courses and by patients on dubious treatment, it may be that it seems to be a particularly attractive gateway to more bizarre alternate treatment philosophies – one that seems to appeal to surprisingly smart and educated dentists.   By granting dentists a license to practice, the public trusts us to apply evidential knowledge to the management of their dental problems. This implies that we must critically examine new hypotheses, decide if there is rational evidence for them, reject the pseudo-science, and apply the knowledge that sifts through for the benefit of the patients we serve.

Post Script:  This is our first article in what we hope will be many to come on dental-related topics.  We would love to hear from you, the fine readers of the Science Based Medicine Blog.  If there are topics you would like to see addressed, or if you have any questions, comments, or critiques, please feel free to email us at  HYPERLINK “mailto:skepticaldentist@gmail.com” skepticaldentist@gmail.com.

Dr. Grant Ritchey received his Bachelor’s degree in Human Biology from the University of Kansas in 1982, and his Doctor of Dental Surgery degree from the University of Oklahoma in 1986. He lives in Kansas City, is married, and has two grown daughters. Since 1986, he has maintained a general dental practice in Tonganoxie, Kansas, and was awarded a Fellowship in the Academy of General Dentistry in 1998. Currently, he is working toward his Masters in Education Degree from the University at Buffalo in the Science and the Public program, with an emphasis on the prevalence of alternative medical practices in dentistry.

Dr. Steve Hendry, BSc DDS FAGD, completed an honours degree in Genetics at the University of Western Ontario before deciding to be a dentist when he grew up. He spent summers working in a corn cytogenetics research lab through dental school. Since graduating in 1981, he’s maintained a general dental practice. Steve has always been fascinated and appalled at the scarcity of critical thinking skills in society and, increasingly in his own profession. He is particularly proud of having attained the status of “closed minded” in the eyes of some of his woo-friendly peers.

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Look here for details. We’ll talk about acupuncture for not too long, and then hang out and drink. Hope to see you there!

KA

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“Strong Medicine”: Ted Kaptchuk and the Powerful Placebo

At the beginning of the first edition of The Web that has no Weaver, published in 1983, author Ted Kaptchuk portended his eventual academic interest in the placebo:

A story is told in China about a peasant who had worked as a maintenance man in a newly established Western missionary hospital. When he retired to his remote home village, he took with him some hypodermic needles and lots of antibiotics. He put up a shingle, and whenever someone came to him with a fever, he injected the patient with the wonder drugs. A remarkable percentage of these people got well, despite the fact that this practitioner of Western medicine knew next to nothing about what he was doing. In the West today, much of what passes for Chinese medicine is not very different from the so-called Western medicine practiced by this Chinese peasant. Out of a complex medical system, only the bare essentials of acupuncture technique have reached the West. Patients often get well from such treatment because acupuncture, like Western antibiotics, is strong medicine.

Other than to wonder if Kaptchuk had watched too many cowboy ‘n’ Native American movies as a kid, when I first read that passage I barely blinked. Although the Chinese peasant may have occasionally treated someone infected with a bacterium susceptible to his antibiotic, most people will get well no matter what you do, because most illnesses are self-limited. Most people feel better even sooner if they think that someone with special expertise is taking care of them. If you want to call those phenomena the “placebo effect,” in the colloquial sense of the term, fine. That, I supposed, was what Kaptchuk meant by “strong medicine.”

Turns out I was mistaken. Let’s briefly follow Kaptchuk’s career path after 1983. In the 2000 edition of The Web, he wrote:

In the almost 20 years since the first edition, I have continued to learn and study. I have treated many patients and worked in many hospitals. I have come into contact with the many other health care systems. For the last ten years I have had a full-time academic appointment at Harvard Medical School (HMS). For four years I worked as a series consultant for a nine-hour British Broadcasting Company (BBC) television series on health care and I was sent to visit various healers on three continents. Currently, I am serving a term on the National Advisory Council of the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health (NIH) where I have the opportunity to contribute to the evolving reconfiguration of America’s pluralistic medical environment.

Kaptchuk used his newfound academic stature to celebrate all sorts of practices in that “pluralistic environment” that had, only a few years before, been widely recognized as quackery. We’ve seen his views on “Chinese medicine”; here, he and co-author (and boss) David Eisenberg wax eloquent on chiropractic:

Treatment by a chiropractor can generate a sense of understanding and meaning, an experience of comfort, an expectation of change, and a feeling of empowerment. Chiropractic’s combination of vitalist “innate intelligence” and simple mechanical explanation can give rich vocabulary for just those illnesses conventional medicine remains poorly equipped to address.

Chiropractors never have to put a patient’s pain in the category of the “mind.” They never fail to find a problem. By rooting pain in a clear physical cause, chiropractic validates the patient’s experience.

Chiropractic is in no sense passive; it is, from the start, engaged. Except when contraindicated (as in patients with neoplastic disease and those with extreme osteoporosis), some form of therapy is almost always indicated. For most symptoms, there is a suitable manipulation or a designated mode of redress.

From the first encounter on, chiropractors generate different expectations from conventional physicians. Because conventional practitioners assume that back pain, in the absence of systemic signs, is likely to be self-limited, it is not unusual for a patient to wait weeks for an appointment with a specialist or for a radiographic diagnostic assessment. Because a chiropractor believes that back pain is both explicable and amenable to treatment, a patient can usually obtain an appointment within 24 hours of a telephone call. The message of empathy, urgency, comprehension, and support conveyed by such a rapid response is reassuring and provides a heightened sense of care and compassion.

Chiropractic’s ultimate lesson may be to reinforce the principle that the patient-physician relationship is fundamentally about words and deeds of connection and compassion. Chiropractic has managed to embody this message in the gift of the hands.

Did the authors realize that they were writing a perfect description of quackery? Apparently not: in the fashion of duplicity-by-euphemism that is standard for quackademia, they refer to the overwhelming evidence that chiropractic is a pseudoscience as “contradictions and tensions [that] exist…between chiropractic and mainstream medicine.”

At some point during the nearly 20 years between the first and second Web, Kaptchuk seems to have begun to wonder if acupuncture and other offerings of ‘various healers’ act via “enhanced placebo effects.” Well, duh. But wait: for Kaptchuk, “placebo” doesn’t mean what it means to me or Mark Crislip or even to Peter Moran or Fabrizio Benedetti. For Kaptchuk, as we’ve already seen, placebo seems to mean something similar to what it means to Daniel Moerman. Placebo is “strong medicine”—maybe even stronger than “Western” medicine. When a trial of “EDTA Chelation Therapy for Coronary Artery Disease” was proposed at a 2000 meeting of the NCCAM Advisory Council,

Dr. Kaptchuk noted that they could find the equivalent of the placebo effect at work here, but both could be more beneficial than conventional therapies…The vote was 11 in favor, none opposed, and two abstentions, so the concept passed for funding.

Thus was spawned the most dangerous, unethical, and expensive boondoggle yet wrought by that August Body, paid for by you and me (Dr. Briggs, are you reading this? Are you, Dr. Nabel?).

Placebo Power and “Power Relationships”: a Post-Modern Deconstruction of the RCT

Kaptchuk’s interest in the placebo seems to have arisen from his displeasure with modern medicine’s ‘privileged’ status, which had presented a barrier to establishing himself as a ‘doctor’ back in the USA. It must have been particularly rankling to take a back seat to the despised, reductionist paradigm, with its insistence on evidence from randomized, often placebo-controlled trials (RCTs). In the 2001 HMS conference to which I alluded at the end of the previous part of this series, Kaptchuk referred to the aforementioned “well, duh” attitude as an “accusation of placebo therapy,” and to “CAM” as a “domain for methodological doubt.” He based this on his suggestion that various “CAM” treatments may have “enhanced placebo effects,” effects that are even stronger than specific biomedical treatments. “Is a placebo effect,” he asked, “only a placebo?” He explains this further in an appendix to the 2000 edition of The Web:

Until about 1955, both East Asian medicine and biomedicine shared similar explicit standards for determining the acceptability of a medical intervention: legitimacy was determined by beneficial outcome. While physicians in both traditions also spoke of medicine based on ‘proven’ or ‘recognized’ principles, and inevitably were influenced by cultural assumptions, acceptable therapy was ultimately expected to deliver relief if not cure.¹

In the years after World War II, biomedicine underwent a dramatic shift. Major reforms were undertaken in medical research that sought to free therapeutic evaluations from human judgment based on clinical experience and impressions…The apparatus of the double-blind randomized controlled trial (RCT) gradually established itself as the ‘gold standard’ for determining legitimate therapy.

A major shift had occurred. A medical intervention was now scientifically justifiable only if it was superior to a placebo: method became more important than outcome. Superiority to placebo replaced ability to confirm health benefits as judgment criteria in medicine. Ideally, an acceptable treatment was now a relative outcome that could be isolated, disguised, and compared to the entire matrix of effects embodied in an identical healing ritual lacking this single ingredient.* Healing was no longer an absolute outcome that comprised multiple interactive dimensions. Biomedicine reconceptualized legitimate healing as “a cause and effect relationship between a specific agent or treatment and a specific biological result” [citation to an article in Medical Anthropology]. Therapeutics that imitated the laboratory and depended on an isolatable, precise, and single mechanism were privileged. For biomedicine, the masked RCT significantly realigned the power relationships between ‘art’ and ‘science’ in medicine, as it was itself a product of this transformation.

*Theoretically, it was now possible for a ‘proven’ drug to have a smaller effect size on a particular ailment than a ‘debunked’ therapy (i.e., an intervention that equals its dummy control).

Footnote 1:

The explicit notion that medicine was acceptable because of positive outcomes was significantly supplemented by the often-unacknowledged process whereby legitimate therapy was determined by prestige, cultural associations, and sociopolitical power relationships. For example, biomedicine was adopted by Asian and African countries most often not because of medical outcomes but because of the prestige associated with the other developments of science. James Nelson Riley provides many examples where ‘the efficacious therapeutic techniques that Western medicine has gathered from modern science have come much more recently than the zeal for promoting science within medicine and for exporting somewhat scientific medicine to other cultures…An ideological commitment to science antedates pragmatic benefits from science.”…For a discussion on how ‘efficacy’ can be seen as a linguistic tool to control medical knowledge, see Elizabeth Hsu, ‘The Polyglot Practitioner [etc.]‘…

In a 1998 article titled “Powerful Placebo: the dark side of the randomised controlled trial,” Kaptchuk characterizes the RCT as “self-authenticating”:

In a self-authenticating manner, the double-blind RCT became the instrument to prove its own self-created value system. This shift from emphasizing outcomes to the purity of the means directly parallels developments in medical ethics where ‘informed consent’ replaced ‘beneficence’ as the pinnacle of the value system.

(Hmmm? He offers no support for the last assertion). In that article he also asserts, with justification, that the premise for the placebo-controlled trial, as advanced by Beecher in 1955,

…took for granted that the active drug response results partly from a placebo effect and that the placebo effect buried in the active arm is identical to the placebo effect of the dummy treatment. The placebo was a single and stable ‘power’ that behaved in a consistent manner.

Kaptchuk, with reason, disagrees with that assumption. With less reason he calls for research to “disentangle the ‘non-specific’ and ‘art-of-medicine’ aspects of healing and therapeutic evaluation.”

In a 2001 article titled “The double-blind, randomized, placebo-controlled trial: gold standard or golden calf?” Kaptchuk again characterizes the RCT as “authenticating itself.” He quotes the philosopher Ian Hacking:

The truth is what we find out in such and such a way. We recognize it as truth because of how we find it out. And how do we know that the method is good? Because it gets at the truth.

In that article Kaptchuk tries to make what might seem, at first glance, a good case for the RCT not being all it’s cracked up to be. He begins with a mildly surprising statement:

Until very recently, there was a widespread perception that the absence of the usual components of the masked RCT will “exaggerate estimates of treatment effects“…It was generally believed that identical treatments “are much less likely to be judged efficacious in double-blind, randomized trials than in uncontrolled case series or unblinded, ‘open’ comparisons with contemporaneous or historical series of patients.”

Yes, but there is still that widespread perception. This “discrepancy argument,” as Kaptchuk calls it, is the basis for the RCT’s sitting atop the Evidence-Based Medicine (EBM) evidence hierarchy, and if it weren’t true it would certainly throw the whole project into disarray. Kaptchuk appears to do exactly that by citing several reviews (here, here, here, here, and here, for example) that “make a compelling case that poor methodology could either overestimate or underestimate treatment effects” (emphasis added). He asserts that such findings have led to a “modified challenge to the discrepancy argument,” such that one study’s authors have argued that “research design should not be considered a rigid hierarchy.” He mentions that the editorial accompanying that and a similar study “has cast doubt on the validity of these conclusions,” without revealing the basis of that doubt; according to Kaptchuk, this shows that “The discrepancy debate has intensified.”

Reading Kaptchuk’s essay you might think, if you were unaware of the crescendo of EBM-chatter in the medical literature over the previous 10 years, that he had discovered a heretofore barely acknowledged, critical, even subversive (as he might put it) Truth about the nature of ‘evidence’ in modern medicine; a truth that would, among other things, liberate “CAM” from the ‘microfascism’ of EBM. Just at that point, however, Kaptchuk adds an afterthought:

In terms of blinding, recent comparative assessments remains [sic] consistent with the older evidence. Three studies showed that double-blind RCTs yielded significantly smaller treatment results than trials that were not double-blind. Also, three studies showed that successful concealment of randomization (compared with inadequate concealment of randomization) produces smaller treatment outcomes. Proper masking seems to create distinct outcomes; the discrepancy argument is intact in this domain.

In this domain? IN THIS DOMAIN? Excuse the yelling, but what “domain” was he talking about in the first place? In other words, after spending about 1000 words trying to convince us that “the usual components of the masked RCT” don’t do what we think they do, he off-handedly mentions that, er, the RCTs that he’d been talking about didn’t have those usual components; meaning, like, they weren’t masked. Which was exactly the point that the mysterious “accompanying editorial” had made.

The discrepancy debate has fizzled. And so, to the satisfaction of most observers, has the “self-authenticating” gambit.

Never mind: in that and other essays, Kaptchuk goes to great lengths to argue that masking, “investigator self-selection,” randomization, informed consent, and other standard research methods introduce “possible systematic errors intrinsic in even an ideal RCT” (in a term reminiscent of another current pseudoscience that closely resembles Quackademia, he dubs this process “irreducible uncertainty”). In this he is undoubtedly correct to an extent, but not to the extent that RCTs must be judged no more valid measures of efficacy than are less rigorous tests claiming larger treatment outcomes. Kaptchuk might protest that he does not explicitly make that claim, but I would respond that he certainly implies it, over and over again.

Kaptchuk is in the company of other influential academic “CAM” advocates, such as Andrew Weil, David Katz, Wayne Jonas, and Mehmet Oz, who’ve been making similar, special pleadings for years.

“The Need to Act a Little More ‘Scientific’ “

We’ve previously heard this from Kaptchuk:

When people became interested in alternative medicines, they asked me to help out at Harvard Medical School. I realized that in order to survive there, one had to become a scientist. So I became a scientist.

I won’t take Kaptchuk too much to task for the obvious faux pas in that statement, even though it is entirely consistent with everything that you’ve read above; he has cultivated a pseudo-bumbling, Columbo-like persona for the purposes of some public presentations, and he came of age during the 1960s, when it was fashionable to be utterly serious while pretending not to be (think: Bob Dylan). So it’s quite possible that he pursued science not merely to survive at Harvard Medical School, but because he hoped to learn something about nature—a ‘domain’ about which, as demonstrated by the first edition of The Web, he’d been quite naive. But did Kaptchuk become a scientist? He seems to have learned a fair amount about clinical trial design and probably a fair amount about frequentist statistical inference. Does that make someone a “scientist” these days? What about nature?

I’m doubtful. In addition to his difficulty in distinguishing science from cultural ‘narrative,’ Kaptchuk stumbles in other fundamental ways. In a 2003 article titled “Effect of interpretive bias on clinical research,” he offers this list:

Definitions of interpretation biases

Confirmation bias—evaluating evidence that supports one’s preconceptions differently from evidence that challenges these convictions

Rescue bias—discounting data by finding selective faults in the experiment

Auxiliary hypothesis bias—introducing ad hoc modifications to imply that an unanticipated finding would have been otherwise had the experimental conditions been different

Mechanism bias—being less sceptical when underlying science furnishes credibility for the data

“Time will tell” bias—the phenomenon that different scientists need different amounts of confirmatory evidence

Orientation bias—the possibility that the hypothesis itself introduces prejudices and errors and becomes a determinate of experimental outcome

Some of his discussion is perfectly reasonable; some is further conflation of science and cultural narrative; some is confusing and even contradictory; some is selective in a way that suggests an agenda:

Good science inevitably embodies a tension between the empiricism of concrete data and the rationalism of deeply held convictions. Unbiased interpretation of data is as important as performing rigorous experiments. This evaluative process is never totally objective or completely independent of scientists’ convictions or theoretical apparatus…

Well, which is it? How can unbiased interpretation be so important if it never happens?

Science demands a critical attitude, but it is difficult to know whether you have allowed for too much or too little scepticism. Also, where is the demarcation between the background necessary for making judgments (such as theoretical commitments and previous knowledge) and the scientific goal of being objective and free of preconceptions?…

Interpretation is never completely independent of a scientist’s beliefs, preconceptions, or theoretical commitments.

Again, which is it? Why propose a goal of being free of preconceptions if scientists always have preconceptions?

Evidence is more easily accepted when supported by accepted scientific mechanisms. This understandable tendency to be less sceptical when underlying science furnishes credibility can give rise to mechanism bias. Often, such scientific plausibility underlies and overlaps the other biases I’ve described. Many examples exist where with hindsight it is clear that plausibility caused systematic misinterpretation of evidence. For example, the early negative evidence for hormone replacement therapy would have undoubtedly been judged less cautiously if a biological rationale had not already created a strong expectation that oestrogens would benefit the cardiovascular system. Similarly, the rationale for antiarrhythmic drugs for myocardial infarction was so imbedded that each of three antiarrhythmic drugs had to be proved harmful individually before each trial could be terminated. And the link between Helicobacter pylori and peptic ulcer was rejected initially because the stomach was considered to be too acidic to support bacterial growth…

Let me explain. Kaptchuk is correct that unbiased interpretation can never happen, so it makes no sense for him to propose otherwise on the same page. Biased interpretation is inevitable, moreover, not merely for the mundane or mischievous reasons that Kaptchuk implies, but because it makes no sense to attempt “unbiased interpretation.” That was shown by Thomas Bayes more than 200 years ago.

Kaptchuk seems to know something about this: in the Comments section he writes, without further explanation, “the arguments presented are obviously compatible with a subjectivist or bayesian framework that formally incorporates previous beliefs in calculations of probability.” If he understands what Bayes demonstrated—that attempting to interpret the results of an experiment without regard to previous knowledge is logically incoherent—he withholds it from his readers, whom he has nevertheless presumed to be largely naive.

My view: if he understood the point when he wrote his treatise, he was dishonest in not explaining it and in not citing at least one pertinent article, such as Steven Goodman’s (which I’m willing to bet he had read). If he didn’t understand the point he should have withheld his paper.

Kaptchuk’s portrayal of interpretive bias being based on “beliefs, preconceptions, or theoretical commitments” implies that such bias is more about cultural assumptions and “power relationships” than about science. That, I believe, is his agenda: to suggest that such ‘commitments’ are likely to ‘privilege’ the status quo and to distract from the truth, thus casting enough doubt on the entire project to give at least a tentative free pass to, well, almost anything.

The reality of science is somewhat different: While it is undoubtedly true that an individual scientist’s biases often reflect personal wishes (not so much cultural assumptions), many of the biases of scientists are not only inevitable, but desirable. Kaptchuk’s discussion of “mechanism bias” is notable for its selection of examples that serve only to condemn such bias. A different sort of example would demonstrate an important truth about science, a truth that Kaptchuk either doesn’t understand or would prefer to conceal from his readers.

Such an example would be a ‘positive’ trial of a claim that, if deemed valid, would require discarding a firmly established principle of nature, such as the 2nd law of thermodynamics—a principle that is not merely a preconception or a “theoretical commitment,” but a fact based on data vastly more rigorous and voluminous than the entire body of biomedical literature. In such a case, not to invoke plausibility would (and has, many times) “cause systematic misinterpretation of evidence.”

The converse of what Kaptchuk calls “this understandable tendency to be less sceptical when underlying science furnishes credibility” is “this understandable tendency to be more sceptical when underlying science furnishes no credibility,” which I would call “good science.” Does Kaptchuk even have a sense of what to look for in a hypothesis? Simplicity, conservatism, fruitfulness, and scope, for example?

Kaptchuk seems to believe his own hype: “method” is more important than science itself. I don’t think that he appreciates, or at least acknowledges, some of the fundamental aspects of science. I also suspect that he isn’t forthcoming about some of the things that he does know, if they don’t suit his agenda.

To be fair, I’ll report that Kaptchuk specifically denies, in the final paragraph of his “interpretive bias” paper, one of the accusations that I’ve made against him:

I do not mean to reduce science to a naive relativism or argue that all claims to knowledge are to be judged equally valid because of potential subjectivity in science. Recognition of an interpretative process does not contradict the fact that the pressure of additional unambiguous evidence acts as a self regulating mechanism that eventually corrects systematic error.

I can’t help but be reminded of another of Kaptchuk’s articles, quoted here a couple of years ago. Its abstract:

The advent of scientific research on complementary and alternative medicine (CAM) has contributed to the current state of flux regarding the distinction between biomedicine and CAM. CAM research scientists play a unique role in reconfiguring this boundary by virtue of their training in biomedical sciences on the one hand and knowledge of CAM on the other. This study uses qualitative interviews to explore how CAM researchers perceive and negotiate challenges inherent in their work. Our analysis considers eight NIH-funded CAM researchers’: (1) personal engagement with CAM, (2) social reactions towards perceived suspiciousness of research colleagues and (3) strategic methodological efforts to counteract perceived biases encountered during the peer review process. In response to peer suspicion, interviews showed CAM researchers adjusting their self-presentation style, highlighting their proximity to science, and carefully ‘self-censoring’ or reframing their unconventional beliefs. Because of what was experienced as peer reviewer bias, interviews showed CAM researchers making conciliatory efforts to adopt heightened methodological stringency. As CAM researchers navigate a broadening of biomedicine’s boundaries, while still needing to maintain the identity and research methods of a biomedical scientist, this article explores the constant pressure on CAM researchers to appear and act a little more ‘scientific’.

Placebo Research: a Critical Positive Impact on Health Care?

What about Kaptchuk having mostly (not entirely) abandoned his advocacy of the purported specific effects of highly implausible medical claims, in the last decade or so, in order to pursue his interest in their non-specific effects? Well, perhaps that has separated him from the rest of the quackpack, to an extent, and for that, some observers feel he deserves credit (Peter?). On the other hand he is no Fabrizio Benedetti, who can call quackery “quackery,” who insists that real, neurobiological placebo effects can’t be studied in clinical trials, not only because of regression to the mean and spontaneous remission, but because of biases introduced by both investigators and subjects (as was likely the case in Kaptchuk’s albuterol vs placebo for asthma trial that triggered this series), and who recognizes that any potential clinical applications beyond the obvious “caring for the patient” are apt to be elusive:

I use the placebo response as a model to understand how our brain works. I am not sure that in the future it will have a clinical application. This is a very important point—a translational research: can we use placebo in routine clinical practice? Well, sometimes it works; but that’s not the important problem. The important thing right now is to understand how our brain works. And I would say the placebo response is a fascinating phenomenon, because it is a sort of melting pot of concepts, of ideas for neuroscience. So, if you use a placebo response, you can understand a lot of brain functions, like anxiety, like social learning, classical conditioning, reward mechanisms, and so forth. So, the clinical application is—I think in English you say it is a ‘different kettle of fish.’

Kaptchuk, on the other hand, in keeping with his belief that the placebo is ‘strong medicine,’ argues that

Learning how to enhance medical outcomes via placebo research could have a critical positive impact on health care and scientific knowledge.

It takes only a bit of perspective to realize that learning how to enhance medical outcomes via placebo research, questionable in itself, is unlikely to have more than a minor impact on health care. That perspective consists of the state of health anywhere in the world prior to the advent of scientific medicine and public health. Kaptchuk, who cut his teeth on “Traditional Chinese Medicine,” might review, in William H. McNeill’s Plagues and Peoples, the appendix titled “Epidemics in China” (part of it can be found here). Does Kaptchuk really believe, or expect the occasional sophisticated reader of The Web to believe, that “biomedicine was adopted by Asian and African countries most often not because of medical outcomes but because of the prestige associated with the other developments of science”?

On Contradiction

For a preview of the final posting in this series, consider these statements:

In clinical practice a sham medical procedure would be fraudulent and deplorable; in research such activities can be legitimate, and this outlying research practice underscores the important ethical differences between clinical trials and medical care.

—Miller and Kaptchuk, “Sham procedures and the ethics of clinical trials”

…both traditional and sham acupuncture were shown to provide clinically significant improvement in back pain and function, as compared with either no treatment or usual medical care, suggesting that the benefit from acupuncture probably derives from the placebo effect. Although this alternative standard for evidence-based validation deserves critical scrutiny and serious debate, we believe that it reflects a more patient-centered perspective for symptomatic treatment. Patients who have continuing pain are interested in pain relief; they are unlikely to care whether this derives from the inherent ability of a treatment to modify pathophysiology or its propensity to promote a significant placebo response.

—Miller and Kaptchuk, letter to the New England Journal of Medicine following the report discussed here, here, and here.

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If you read enough supplement advertisements, like I do, you’ll often see the purity of  a product often cited as one of its merits. It’s usually some phrase like:

Contains no binders! No fillers! No colours! No excipients! No starch! No gluten! No coatings! No flow agents!

It’s a point of pride for supplement manufacturers to advertise that their product contains nothing but the labelled ingredient. And that’s also seen as an important benefit to many that purchase supplements. The perception from many consumers (based on my personal experience) seems to be that products are inferior if they contain non-drug ingredients. By this measure, drug products are problematic. Pharmaceuticals all contain an array of binders, coatings, supplements and fillers.  Even (gasp) artificial ingredients and sweeteners! And they’re often, though not always, disclosed on the package label.

But rather than being a negative feature, these supplementary, non-medicinal ingredients play a critical role in ensuring that drug products are of consistent and reproducible quality. Without them, we’d have products that are potentially unstable, we’d be unclear if they were actually being absorbed, and we wouldn’t know if they actually delivered any active ingredients into the body. In short, we’d be in the same situation we’re currently in with many herbal remedies and other types of supplements.

Standard pharmaceutical products are evaluated in both clinical trials (to measure efficacy) but also more basic tests – such as whether a drug that is ingested is actually absorbed into the bloodstream.  A promising drug won’t work if it doesn’t reach the desired site of action. And to do that, we use a variety of tools and processes to ensure that a drug is reliably and predictably absorbed when we use it, whether by ingesting it, rubbing it on our skin, or injecting it. Excipients can be described as any components of a drug product that are not the “API”, the active pharmaceutical ingredient. Excipients serve to keep the API stable, help its absorption, and simplify the manufacturing process.They help ensure that products are consistent – batch to batch and bottle to bottle. Excipients also help improve consumer acceptance and usage.

It took me some time as a pharmacist before I realized why  supplement manufacturers strive to minimize the use of excipents in their products. It’s because the consistency, absorption and effectiveness of most products hasn’t been measured, and doesn’t need to be evaluated. That is, there’s no testing done to see if the product is absorbed consistently. You can’t control what you don’t know, and with the majority of herbal products, there’s no standardization of  the active ingredient – because it may not even be clear what the active ingredients actually are. So any attempt to produce a consistent product is complicated by the lack of an API, and not knowing what type of product consistency is needed.

I’m asked about excipients regularly. There are hundreds in use, and their presence can be confusing to consumers, who may not understand their role. Patients may also have personal concerns about a specific type of excipient, or may need to avoid specific substances due to allergies. Here are some of the inactive ingredients you may see listed on on a package’s label – and why they’re there:

Fillers/Diluents/Bulk Materials

To make dosage forms a reasonable size, bulk materials are added to give size to finished products. (Imagine the size of a 100 microgram tablet without any fillers). Bulk materials also ease processing and manufacturing. They may influence the flow of the material during manufacturing, and can impact on the final product’s stability.  Typical fillers for tablets and capsules include starch, calcium salts, and sugars like lactose.  In liquid formulations, materials like glycerine and water are used to dissolve (or suspend) active ingredients and simplify dose measurements.  Alcohol, a historically popular diluent, is now rarely used. Topical products like creams and lotions use fillers like mineral oil, petrolatum, lanolin and various waxes.

Lactose is a common filler and sweetener (see below) in many prescription and non-prescription drugs. While intolerance is possible, the small amounts in most drugs makes the risk minimal.

Coatings and Disintegrants

Once the dosage form is consumed, we want it to dissolve in a consistent manner. Products that don’t dissolve are not absorbed. Disintegrants break up a tablet or capsule at the appropriate time.  Most orally consumed APIs are stable in stomach acid and disintegrate within a few minutes of ingestion. Some can be absorbed under the tongue, so disintegrating agents ensure that products like nitroglycerine dissolve immediately upon contact with saliva.   Common disintegrating agents include alginic acid, microcrystalline cellulose, and various forms of starch.

Coatings provide protection of the final product from light, oxygen, and moisture. Coatings can include gluten, (food grade) shellac, and gelatin. Some drugs are destroyed by stomach acid, so a combination of coatings and disintegrants ensure they dissolve late, after the intact tablet has passed into the small intestine, a less acidic environement. Acid-resistant (“enteric”) coatings, like cellulose acetate phthalate, work this way. That’s why some products must not be crushed or chewed before swallowing: The active ingredient would otherwise be destroyed by stomach acid.

Lubricants

Lubricants are incorporated into dosage forms to support the manufacturing process. They can reduce static charges, and ease the flow of the powder form, ensuring products will have a consistent content of the API per unit. Lubricants impact on the dissolution of the final dosage form, affecting the absorbtion rate and extent. Lubricants include calcium and magnesium stearate, polyethylene glycol, stearic acid, and talc.

Sweeteners and Flavoring Agents

Sweetener products and flavoring agents make final products palatable. If you’ve ever tried to give a child a foul-tasting medication, you already have an appreciation of palatability.  Palatability means that people will take their medication – a basic yet critical component of science-based medicine. In solid oral products, like tablets, sweeteners and flavors may coat tablets. In liquid products, like syrups and suspensions, sweeteners include sugars, artificial sweeteners, and products like corn syrup. Natural sweeteners are generally less popular from a manufacturing perspective, because of their association with dental caries, and possible impact on diabetics.  Flavoring agents can be naturally-sourced or synthetically created. There is no intrinsic advantage to a natural sweetener or flavoring agent – it’s the physical characteristics that are important, not its origin.

Coloring Agents

Colours help with product identification and are also used for consistency with flavors, particularly in children’s formulations. (Though I truly didn’t appreciate the “dye-free” versions until I had a mouthful of a medication sprayed on me by an unhappy child.)  In general, children and adults have no problems with the tiny amounts of dyes and colors in pharmaceutical products, though reactions have been reported, particularly with  the product tartrazine.

Preservatives

Preservatives can stabilize the active ingredient or ensure a product remains sterile, which is a concern with all injectables and aqueous (water-based) products. Thimerosal needs no introduction to SBM readers. It’s a vaccine preservative. Benzalkonium chloride is a common preservative in contact lens products.

Allergies to Excipients

Adverse reactions and allergies can occur to both medicinal and non-medicinal ingredients. Severe allergic reactions have been attributed to trace amounts of corn in a dosage form [PDF], for example.  The management of allergic reactions involves closely checking all excipients (and their sources), and isolating the causative agent (if possible). It can take a lot of digging, and sometimes even specialized pharmacy compounding, to deal with severe allergies and intolerances to commonly-used excipients.

The Product Expiry Date
Expiry dates for products are based on when a product’s finished quality standards (e.g., strength, quality, purity) are no longer met. That is, when product degradation progresses to a point where the product either lacks the labelled potency (most cases) or in some cases, has degraded into compounds that may be toxic. Chemicals can deteriorate for reasons that include chemical reactions, such as oxidation (usually from exposure to air or moisture), physical changes (e.g., separation of a suspension), photochemical reactions (i.e., light exposure) and even chemical reactions with the product packaging. Quantitative analysis of newly prepared products is done, usually in the final packaging, to understand how quickly a product will deteriorate, and the expiry date is established based on this information. This can be an iterative process – the final product formulation may change to make a product more stable. Or the packaging may change to give the finished product a longer shelf-life. Multiple factors can play a role.

Conclusion

Excipients play an important role in ensuring that medications are consistently absorbed and reproducible in their effects. Consumers should be reassured that their inclusion actually improves, rather than detracts from, the quality of the finished product.

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The discovery of various vitamins – essential micronutrients that cause disease when deficient – was one of the great advances of modern scientific medicine. This knowledge also led to several highly successful public health campaigns, such as vitamin-D supplementation to prevent rickets.

Today vitamins have a deserved reputation for being an important part of overall health. However, their reputation has gone beyond the science and taken on almost mythical proportions. Perhaps it is due to aggressive marketing from the supplement industry, perhaps recent generations have grown up being told by their parents thousands of times how important it is to take their vitamins, or eat vitamin-rich food. Culture also plays a role – Popeye eating spinach to make himself super strong is an example this pervasive message.

Regardless of the cause, the general feeling is that vitamins are all good – they are not only important for health, they promote health. Many people take vitamin supplements on the idea that more is better, or for nutritional “insurance” to make sure they are getting enough of every vitamin.

The problem with deeply embedded cultural beliefs is that people make decisions based upon assumptions that everyone “knows,” rather than making evidence-based risk vs benefit decisions. This phenomenon is exacerbated when the industry is able to make aggressive health claims without requiring any scientific evidence to back up those claims (as is the case in the US since DSHEA was passed in 1994).

It is therefore important to shatter the pedestal on which vitamins have been placed, to bring them down to the level of scientific evidence. The good news is, there is a ton of research on vitamins, which continue to be the subject of much new research. Each year, therefore, the risks and benefits of vitamins become more clear. One recent study which is getting much press adds to this body of knowledge about vitamins.

In the latest issue of The Archives of Internal Medicine is a population based observational study looking at health outcomes and vitamin use as part of the larger Iowa Women’s Health Study. The authors looked at 38,772 older women and asked them to self-report their vitamin use. This is a long term study and their vitamin use was reports in 1986, 1997, and 2004, and mortality was followed through 2008. They found a small but statistically significant increase in mortality for those taking multivitamins, B6, folic acid, iron, copper, magnesium and zinc. There was also a small decrease in mortality for those taking calcium.

The strength of this study is that it is large with a long term follow up. There are many weaknesses, however. Vitamin use was self-reported. Further, this is a correlational study only. Therefore possible confounding factors could not be controlled for. For example, it is possible that women who have an underlying health issue that increases their mortality were more likely to take vitamins or to report taking vitamins.In fact, other studies suggest there is such a “sick-user effect” with vitamins.

It is therefore not possible from this study to draw any conclusions about cause and effect – that vitamin use increases mortality. But it does provide a cautionary reminder that it is not reasonable to assume that vitamin supplementation is without any risk. We still need to follow the evidence for the use of specific vitamins at specific doses for specific conditions and outcomes.

Conclusion

As is typical of observational studies, the results are somewhat mixed, depending upon the details of how such studies are conducted. There are also many variables to consider – which vitamins and which doses in which populations with what health conditions. There is therefore a great deal of noise in the data. I do not think we can conclude that the vitamins listed above actually increase risk of mortality. But neither can we conclude that there is any health benefit for routine supplementation. Years of research have failed to provide such evidence, and the mixed results we are seeing is consistent with there being no or only a small effect.

Based upon the totality of evidence the best current recommendation is to have a well-rounded diet with sufficient fruits and vegetables, which should be able to provide most people with all the micronutrients they require. There is no evidence to support routine supplementation. There is also reason to avoid taking megadoses of vitamins, as this can cause toxicity, and even short of toxicity the evidence becomes more compelling at higher doses of the risks of supplementation.

But there are also many situations in which targeted supplementation is evidence-based and appropriate. There is increasing evidence to support the use of vitamin D supplementation for many populations. Many elderly have borderline or  low B12 levels, which correlates with dementia. Pregnant women should take prenanatal vitamins. (To give just a few examples.)

Vitamins are just like any other health care intervention – they have potential risks and benefits and it is best to follow the evidence. For most people the best advice is to ask your primary health care provider which supplements, if any, you should take. Recommendations should be based upon specific health conditions and blood tests to measure levels of vitamins, so that specific deficiencies can be appropriately targeted.

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I’m fed up! In August 2009 I wrote about Protandim, pointing out that it’s not supported by good evidence. I thought I had made myself clear; but apparently I had only made myself a target. True believers have deluged the Internet with attacks on my article, calling it mere “opinion,” ignoring its main points, and denigrating me personally. I have ignored the Internet attacks, but I’m beginning to feel personally harassed: I have lost count of the e-mails I have received from Protandim enthusiasts trying to convince me that it works and that I should change my mind. I’ve spent hours trying to explain my reasoning in e-mails, and it’s becoming a repetitive chore, so I am writing this so that next time I get an e-mail inquiry I can simply forward this link.

What Is In It?

Protandim is a mixture of milk thistle, bacopa extract, ashwagandha, green tea extract, and turmeric extract (all of which, incidentally, can be purchased individually at much lower cost).

What Do They Claim It Does?

As described on Wikipedia:

The manufacturers of Protandim claim the product can indirectly increase antioxidant activity by up-regulating endogenous antioxidant factors such as the enzymes superoxide dismutase (SOD) and catalase, as well as the tripeptide glutathione, and by activation of theNrf2 pathway.

Nrf2 is a transcription factor that upregulates the expression of various genes that may regulate oxidative stress. Drugs to target that pathway might have benefits for diseases that are caused or exacerbated by oxidative stress. Such drugs are investigational at this point, but the makers of Protandim have skipped the investigational stage and are marketing a product that they think is effective for almost every ailment known to man and that they are promoting as an anti-aging supplement.

In the application for their second patent, awarded in 2008, they wrote:

The compositions of the present invention are useful to prevent or treat the following disorders and diseases: memory loss; Parkinson’s disease; aging; toxin-induced hepatotoxicity, inflammation; liver cirrhosis; chronic hepatitis; and diabetes due to cirrhosis; indigestion; fatigue; stress; cough; infertility; tissue inflammation; cancer; anxiety disorders; panic attacks; rheumatism; pain; manic depression; alcoholic paranoia; schizophrenia; fever; insomnia; infertility; aging; skin inflammations and disorders; alcoholism; anemia; carbuncles; convalescence; emaciation; HIV; AIDS; immune system problems; lumbago; multiple sclerosis; muscle energy loss; paralysis; swollen glands; ulcers; breathing difficulties; inflammation; psoriasis; cancer (e.g.; prostate cancer, lung cancer and breast cancer); pain; cardiovascular disease (e.g.; arteriosclerosis and atherosclerosis); ischemia/reperfusion injury; anxiety; attention deficit disorder; leprosy; arthritis (e.g., psoriatic arthritis; ankylosing spondylitis; and rheumatoid arthritis); hemorrhoids; tuberculosis; high blood pressure; congestive heart failure; venous insufficiency (pooling of blood in the veins; usually in the legs); sore throat; hepatitis; syphilis; stomach ulcers; epilepsy; diarrhea; asthma; burns; piles; sunburn; wrinkles; headache; insect bites; cuts; ulcers; sores; herpes; jaundice; bursitis; canker sores; sore gums; poison ivy; gastritis; high cholesterol; heart disease; bacterial infection; viral infection; acne; aging; immune disorders; dental caries; periodontitis; halitosis; dandruff; cardiovascular disease (e.g., hypertension; thrombosis; arteriosclerosis); migraine headaches; diabetes; elevated blood glucose; diseases of the alimentary canal and respiratory system; age-related physical and mental deterioration (e.g., Alzheimer’s Disease and age-related dementia); cardiovascular disease; cerebral vascular insufficiency and impaired cerebral performance; congestive symptoms of premenstrual syndrome; allergies; age-related vision loss; depression; Raynaud’s disease; peripheral vascular disease; intermittent claudication; vertigo; equilibrium disorder; prevention of altitude sickness; tinnitus (ringing in the ear); liver fibrosis; macular degeneration; asthma; graft rejection; and immune disorders that induce toxic shock; bronchpulmonary disease as cystic fibrosis; chronic bronchitis; gastritis; heart attack; angina pectoris; chronic obstructive pulmonary disease; kidney damage during coronary angiography; Unverricht-Lundborg disease; pseudoporphyria; pneumonia; and paracetamol hepatotoxicity.

Wow! Yet the website says it “does not market and sell Protandim® for the purposes of preventing, treating, curing, or mitigating any disease, including MS.”

So what purposes are we to think they do market and sell it for? Since oxidation is thought to be somehow involved in all the listed conditions, they are speculating that Protandim should prevent or treat those diseases by increasing the body’s production of antioxidants. They are promoting it for “anti-aging” because they are speculating that it will prevent or treat age-related diseases. They have no credible evidence to support their speculations.

An Update of Their Evidence

My original article only mentioned the 3 studies available at that time. As of this writing (October 2011), a query to PubMed brings up 8 published, peer-reviewed studies:

1. A human study showing changes in TBARS, SOD, and catalase.(2006)
2. A cell culture study showing increases in glutathione. (2009)
3. A mouse study showing an effect on skin tumor carcinogenesis. (2009)
4. A study in a mechanical animal model showing that chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. (2009)
5. Another mouse study showing that Protandim suppressed experimental carcinogenesis and suggesting that suppression of p53 and induction of MnSOD may play an important role.  (2010)
6. A study of muscular dystrophy mice showing that Protandim decreased plasma osteopontin and improved markers of oxidative stress. (2010)
7. An ex vivo (tissue culture) study of human saphenous veins, showing that Protandim attenuated intimal hyperplasia. (2011)
8. An evaluation of the role of manganese superoxide dismutase in decreasing tumor incidence in a two-stage skin carcinogenesis model in mice. (2011)

Note that there have been no human clinical studies since the one in 2006. The newer studies are just more animal and laboratory studies, so they do nothing to change my previous conclusion.  If I were a mouse being artificially induced to develop skin cancer in a lab study, I might seriously consider taking Protandim.  But so far, the only study in humans measured increased antioxidant levels by a blood test but did not even attempt to assess whether those increases corresponded to any measurable clinical benefit, for cancer or for anything else.

My Assessment of the Evidence

This sounds like a promising area of investigation, but many treatments look promising in animal and in vitro (test tube) studies in the lab and then fail to translate to any useful clinical applications in humans. Much has been said about the benefits of antioxidants, but giving antioxidants as supplements has generally resulted in no benefits and even sometimes in harm. Protandim is trying another approach: getting the body to produce more of its own antioxidants. Even if it does that, it still remains to be seen whether those higher levels will correspond to any meaningful clinical benefits. And the tests they are using for antioxidant levels may not mean what they would like to think they mean. Sometimes the same substance can show either anti-oxidant or pro-oxidant effects depending on which test is used. And adverse consequences haven’t been ruled out. Free radicals play important roles in human health: they are essential for killing bacteria, cell signaling, and other functions. Raising antioxidant levels might interfere with some of these essential functions. Human biochemistry is complex, and changing one factor often has unexpected effects elsewhere in the web.

Conclusion

We simply don’t know enough at this point to recommend Protandim for treatment or prevention of any disease, for anti-aging, for making people feel healthier or more energetic, or for anything else. We need good human studies showing that people who take Protandim have better clinical outcomes than people who don’t. For instance, fewer heart attacks or fewer cancers…not just higher levels on a TBARS test. What we need is POEMS: patient-oriented evidence that matters.

I Get Mail

I heard from doctors working with the company, from company employees, from distributors, from customers, from relatives of customers, and even from people who were none of the above. Most of my correspondents completely failed to understand what I meant by human studies with meaningful clinical outcomes. Some of them thought I was not aware of the published evidence. Some of them wanted to insult me and the whole medical profession. Some offered testimonials. One wanted to revise the Hippocratic Oath. Others wanted to inform me that Protandim had been awarded patents and that its shares were doing well on the stock market. Some were more coherent than others. Here’s a sampling (errors in the original):

• My wife has stage 4 metastatic breast cancer, a friend was telling about a natural supplement called Protandim. I was thinking about buying it after he showed me a study from LSU that says is maybe helpful in fighting cancer. I just ran across your blog and you say it is a scam. I am wondering if you are familiar with the LSU study
• Did LSU not just present evidence that TBAR reduction with Protandim led to a meaningful clinical outcome?.. Regarding glutathione’s potential efficacy: go to youtube and search Dr. David perlmutter. Check out the before and after videos of Parkinson’s patients being injected with glutathione… Protandim is unique in having extensive scientific validation published in our most well respected, peer reviewed journals..
• How do you feel about Protandim now that it has a clinical study?
• I was impressed that Dr Perlmutter and Dr Colker both endorse protandim. What about the recent peer reviews on Cancer and Heart disease as well as the one on Glutathione?
• Purpose of the email is to entice, I hope, you into taking a closer look at Protandim… Publishing a negative opinion will impact these people and if you are wrong and Dr. McCord is correct, there are a number of people who will not benefit from what is considered by a growing number of scientists to be cutting edge science in ageing and disease prevention.  My opinion is that you would benefit from getting up to speed in this arena.
• You quackbusted on a Protandim back in 2005.  I’m wondering if you still feel the same about Protandim and Dr Joe McCord now that it’s 5 years later???  I was just made aware of protandim and wanted to know more because everything I am seeing is pointing me in the direction of yes you should be taking the stuff!!
• Obviously there are 2 sides to what is going on here and I’m quite disturbed with the medical community and the belief that it’s their way or the highway and that the human body isn’t capable of fixing itself as Gerson explains it!!  I have been on the Protandim for 3 weeks tomorrow just 1 supplement a day and I feel a difference in my knees and ankles with a little more kick when going up the stairs…I’m actually bouncing a lot better than I was 3 weeks ago…I’m still on a 12,000 ORAC Unit intake so nothing has changed except the protandim supplements…it appears I’m experiencing the same thing I am seeing/hearing from the others!!
• you stille hold that opinion after the new studies ?How can you explain the fact that many universities fundind their own research ?Is dr Pearlmuter that endors protandim will risk his reputation if it is not the real deal
• Protandim was up 10% yesterday on volume of 177,000.  Another step in the right direction.
• (paraphrased) My friend’s lipid peroxidase levels rose; here’s his lab report to prove it.
• proven by peer reviewed, published scientific research to reduce oxidative stress by an average of 40%, slowing down the cellular aging process to that of a 20 year-old!
• I accept your views and beliefs for they are yours, and who am I to disagree?  I do have a couple points to voice which may offer some advice on confirming whether a product is legitimate or fake….I notice that you mentioned because something is not FDA approved that it must therefore be quackery.  Again, this is your belief, so ok…. Herbs have been used in medicines around the world, successfully, and for thousands of years…prior to Western medicine.  The FDA and many doctors here in the ‘West’ are unsure of these remedies and this causes fear.  Ego, a human trait, can also get in the way.  It’s just our nature.” (this was from someone who has yet to try the product but plans to do so soon)
• that’s the problem with modern medicine.  they are challenged by something, so incredibly, that they would rather eliminate it than find perhaps a new direction for health and medicine.   Ego?  Fear?
• btw, you know an underlying problem in medicine today?  the hippocratic oath.   “First, do no harm.”    The reason this needs to be improved is because that oath has the words:  ‘no’ and ‘harm’ in it.   Modern psychology today will confirm that our brains really only focus on the key words, rather than a ‘no’ or ‘dont’ that precedes a statement.
• Harriet, have you ever challenged any modern medicine, Lipitor as an example? Or any so called modern medicine?
• I am not against allopathic medicine, however, I feel that our bodies work better with organic natural medicine.
•  while I share some of your concerns, I feel that the house is burning and something must be done for our poorly aging population.
• Just wanted to make you aware that Protandim received its 4th patent.”Compositions for alleviating inflammation and oxidative stress in a mammal
• I have tons of them [clinical studies] , I have MD ‘s by the tons getting involved . I have clients getting of MEDs , cholesterol , Bp’s. Insulin cut in half , sleep apnea gone, chronic fatigue gone. Should I listen to results and MD’s and Using Godly wisdom or your bashing and other people see a nutritionist’s opinion as important. Thanks any way ms. Hall”
• “It more than establish’s things when people’s lives have been changed. I didn’t see your name on the winners of the Elliot Cresant award hince , Joe McCord . Last time I checked all my clients were humans . All of them have been on for 4 months or more so there is no placebo affect. Oh and I trust the holy spirit more than all the above things. Thanks
•  I have read some of your older write-ups about Protandim… it seems many are dated 2005.  Surely by now you have changed your mind about Protandim. The proof it works is now everywhere. I have seen many benefits myself and my wife has finally got her sugar levels under control by doing nothing other than take Protandim.  I do not sell this nor own stock in the company but I try to get as many people on this as I can… because it works. Are you on board or are you still against Protandim?

One Skeptical Message

I did get one message (only one) that was skeptical about Protandim. It pointed out further problems with the research:

Both Protandim and Mona Vie site numerous peer reviewed, published studies that support their claims. Upon basic investigation you will see that all the peer review studies are lead by the same shareholder / researcher (One for Mona Vie and One for Protandim). Shouldn’t this obvious conflict be a red flag for the peers that are reviewing? In addition for Protandim products most of the papers were published in one journal of which that lead researcher is also an editor. The only other journal they were published in is Plos One which appears to be an open access online journal with a very high publish rate per submission (I read 98%).

A message to Protandim supporters

I am not “against” Protandim. I would be very pleased if it turns out to improve people’s health. I await clinical research with great interest. I would not take it myself or recommend it at this time because I have seen too many initially promising treatments turn out not to work or even to cause harm.  I understand why some people are enthusiastic about Protandim and want to take it now rather than wait for better evidence, and I have no objection to their taking it. I am not “quackbusting;” I am only asking for the same kind of evidence that the scientific community requires before it accepts any new treatment. Please try to understand what I mean by clinical studies with meaningful outcomes and contact me again when such studies are available… and not before.

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An Apple fanboy contemplates computers and mortality

I’m a bit of an Apple fanboy and admit it freely. My history with Apple products goes way back to the early 1980s, when one of my housemates at college had an Apple IIe, which I would sometimes use for writing, gaming, and various other applications. Indeed, I remember one of the first “bloody” battle games for the IIe. It was called The Bilestoad and involved either taking on the computer or another opponent with battle axes in combat that basically involved hacking each other’s limbs off, complete with chunky, low-resolution blood and gore. (You youngsters out there will be highly amused at the gameplay here.) Of course, it’s amazing that nothing’s changed when it comes to computer games except the quality of graphics. Be that as it may, this same roommate was one of the first students to get a hold of the new Macintosh when it was released in early 1984. I really liked it right from the start but only got to play with it occasionally for a few months. After using a Macintosh SE to do a research project during my last year of medical school, I have used the Macintosh platform more or less exclusively, and the first computer I purchased with my own money was a Mac LC back in 1990 or 1991. Today, I have multiple Apple products, including my MacBook Air, my iPhone, and my old school iPod Classic, among others. Oddly enough, I do not have an iPad, but that’s probably only a matter of time, awaiting software that lets me do actual work on it.

All of this is my typical long-winded way of explaining why I was immensely saddened when I learned of Steve Jobs’ death last week. Ever since speculation started to swirl about his health back 2004 and then again in 2008, capped off by the revelation that he had undergone a liver transplant for a rare form of pancreatic cancer in 2009, I feared the worst. Last week, the end finally came. However, there is much to learn relevant to the themes of this blog in examining the strange and unusual case of Steve Jobs. Now, after his death five days ago, which coincidentally came a mere day after the launch of iCloud and the iPhone 4S, it occurs to me that it would be worthwhile to try to synthesize what we know about Jobs’ battle with cancer and then to discuss the use (and misuse) of his story. Of course, this is a difficult thing to do because Jobs was notoriously secretive and I can only rely on what has been published in the media, some of which is conflicting and all of which lacks sufficient detail to come to any definite conclusions, but I will try, hoping that the upcoming release of his biography by Walter Isaacson in couple of weeks might answer some of the questions I still have remaining, given that Isaacson followed Jobs through his battle with cancer and was given unprecedented access to Jobs and those close to him.

In the meantime, I speculate. I hope my speculations are sufficiently educated as not to be shown to be completely wrong, but they are speculations nonetheless.

Jobs and pancreatic cancer

Back in 2003, Jobs was flying high. Ousted from Apple in 1985 and then brought back in 1997, over the last six years he had brought the company back from the brink of bankruptcy, first with the launch of the iMac and then a few years later with the wildly successful iPod. It was at this time that he received news that no one wants to hear. Having recently undergone an abdominal CT scan, a mass had been found in his pancreas, apparently at the head of the pancreas.

Now, for all the reports I’ve read of this initial diagnosis, it’s utterly unclear to me exactly what the indication for the scan was, and at the time Jobs’ diagnosis was shrouded in secrecy. It wasn’t until 2008 that an article was published in Fortune entitled The Trouble With Steve Jobs and described his diagnosis thusly:

During a routine abdominal scan, doctors had discovered a tumor growing in his pancreas. While a diagnosis of pancreatic cancer is often tantamount to a swiftly executed death sentence, a biopsy revealed that Jobs had a rare — and treatable — form of the disease. If the tumor were surgically removed, Jobs’ prognosis would be promising: The vast majority of those who underwent the operation survived at least ten years.

So, right from the beginning, SBM bumped up against how Jobs was treated, as even now, the indications for “routine” abdominal CT scanning in an otherwise healthy man in his late 40s are virtually nonexistent, as Sharon Begley points out in an article published last week:

He reportedly had the scan — which is seldom done, much less advised, as a routine part of a physical — because he had a history of gastrointestinal problems, but he also may have been experiencing symptoms, most likely gastrointestinal ones.

Whatever the reason Jobs underwent a CT scan, either “routine” (which is almost never indicated) or for vague symptoms (for which the indication might have been weak but not nonexistent). At the time, Jobs would appear to have been incredibly lucky in two ways. First, he was lucky in that his tumor was discovered by what would in the absence of clear cut symptoms normally be a very low-yield test that exposes patients to both the risk of intravenous contrast and radiation exposure. These risks are quite low, but difficult to justify without clearer indications. However, CT scans are frequently overused in this country, and it is not surprising that Jobs underwent one for “soft” indications; it’s just that this time he was the exception, with disease detected early, rather than the rule, where the scan usually finds nothing helpful. Secondly, a biopsy of the lesion demonstrated that it was not the much more common (and deadly) form of pancreatic cancer, adenocarcinoma, which arises from the ducts of the pancreas, is rarely cured, and generally produces a median survival of less than a year. Rather, he had the much less aggressive form of pancreatic cancer, a neuroendocrine tumor. These tumors are often indolent and slow-growing. Unfortunately, they also tend to secrete hormones, which also tend to be responsible for most of the symptoms they cause. In Jobs’ case, it was insulin and his tumor was an insulinoma. Although, again thanks to Jobs’ secrecy, we have no idea what symptoms he was experiencing at the time, insulinomas typically result in a profound drop in blood sugar, and this hyperinsulinemia can lead to symptoms of insulin shock, such as tremors, cold sweats, nausea and vomiting, blackouts, and neurological symptoms such as confusion, apathy, and irritability.

Whatever Jobs’ talents, it became obvious that one of them was not good judgment about medicine. Whatever his business and design savvy, when it came to medicine, he demonstrated critical thinking skills that, if applied to his business dealings, would bring Apple down from its heights to utter ruin. Neuroendocrine tumors of the pancreas make up less than 2% of all pancreatic tumors, and he was lucky enough to have gotten that form rather than the more common deadly version. Surgery would have a high probability of curing him.

Here’s more of the story:

But Jobs sought instead to treat his tumor with a special diet while launching a lengthy exploration of alternative approaches. “It’s safe to say he was hoping to find a solution that would avoid surgery,” says one person familiar with the situation. “I don’t know if he truly believed that was possible. The odd thing is, for us what seemed like an alternative type of thing, for him is normal. It’s not out of the ordinary for Steve.”

Apple director Levinson, who has a Ph.D. in biochemistry, monitored the situation for the board. He and another director, Bill Campbell, tried to persuade Jobs to have the surgery. “There was genuine concern on the part of several board members that he may not have been doing the best thing for his health,” says one insider. “But Steve is Steve. He can be pretty stubborn.”

If it was fear that motivated Jobs, I can understand it. Although he was fortunate enough to have an islet cell cancer instead of the more common and deadly adenocarcinoma of the pancreas, it was in the head of the pancreas, the part that is closest to the duodenum. Lesions in the tail of the pancreas can often be removed with an operation called a distal pancreatectomy, which involves removing only part of the pancreas. Because of the anatomy of the head of the pancreas, its attachment to the duodenum, and the blood vessels in the area, the only way to remove lesions in the head of the pancreas is to do a much larger operation known as a pancreaticoduodenectomy, or, as it is more commonly known, the Whipple operation. There are a lot of potential complications to a Whipple operation. Sometimes, we weigh those complications and how long they would keep a patient in the hospital, against how long a patient has left. If a pancreatic cancer patient has only a few months left, doing an operation that will have him spending a significant chunk of his brief remaining time left in the hospital is a real consideration. However, that wasn’t a consideration for Steve Jobs. He would very likely be cured by the surgery. Moreover, in competent hands, the complication rate from a Whipple is acceptable, particularly if the patient is otherwise healthy. Even though the article quotes a 5% mortality rate, that is usually in the case of patients with pancreatic adenocarcinoma, most of whom tend to be somewhat debilitated to start with due to the tumor. It would probably have been less in Jobs’ case. True, because the duodenum is removed, another expected sequela of the operation is, depending on whether the pylorus is spared, having to eat a diet like that of patients who have their stomachs (or large portions thereof) removed (more on that later)

This is not a controversial issue in medicine; there is no other effective treatment for these neuroendocrine tumors:

By the standards of medical science, it was an open-and-shut case: There was no serious alternative to surgery. “Surgery is the only treatment modality that can result in cure,” Dr. Jeffrey Norton, chief of surgical oncology at Stanford, wrote in a 2006 medical journal article about this kind of pancreatic cancer. It was Norton, one of the foremost experts in the field, who eventually operated on the Apple CEO, Fortune is told. (He declined to comment.)

Dr. Roderich Schwarz, chairman of surgical oncology at the University of Texas Southwestern Medical Center in Dallas, who has performed the procedure more than 150 times (but who was not involved in Jobs’ case), says that waiting more than a few weeks with this diagnosis “makes no sense because you don’t know what the potential for growth or spread is.” Schwarz says he knows of no evidence that diet can be helpful. “But the patient decides. If they believe an herbal diet can do miracles, they have to make the decision. Every once in a while you have somebody who decides something you wish they wouldn’t.”

I couldn’t resist including this quote because Rod used to be one of my partners back in the day when I worked at The Cancer Institute of New Jersey. In any case, even though insulinomas tend to be indolent, waiting nine months to undergo surgery was probably not the best idea. It might not have hurt him (or it might have), but it certainly didn’t help (more on that later). Nowhere have I been able to find a detailed description of how large the tumor was upon its discovery or by how much it grew during those nine months. Whatever the case was, the surgery was apparently a success, with complete removal of the tumor.

For four years, Jobs appeared to do quite well after that.

Complications of the Whipple operation or something more dire?

In June 2008, Apple introduced the iPhone 3G, its second-generation iPhone. When Jobs took the stage to dazzle the crowd with his usual aplomb, many in the audience were shocked at his gaunt appearance. Soon after, it was revealed that he had undergone a second surgical procedure to reverse some nutritional issues related to his first surgery.

At the time, I thought I knew what might be going on. Jobs underwent a Whipple operation, more correctly referred to these days as a pancreaticoduodenectomy. This is a huge operation, one of the biggest and most radical rearrangements of a patient’s anatomy that is done routinely. What’s done is that the head of the pancreas and duodenum are removed en bloc (mainly because their close proximity to each other and their shared blood supply make it virtually impossible to remove the pancreatic head alone). This tour de force operation then necessitates putting things back together thusly:

There are many potential complications of the Whipple procedure, because it’s a big operation and it’s an operation on the pancreas. There’s a famous saying in surgery that goes, “Eat when you can, sleep when you can, but don’t mess with the pancreas.” (Usually another, far less savory word than “mess” is used.) In any case, there are almost always long term nutritional consequences that derive from rearranging a patient’s anatomy in so radical a fashion. First off, patients almost always lose 5-15% of their body weight right off the bat, although that usually levels off fairly quickly. Jobs, however, was never exactly what you would call robust-looking. He was always on the thin side; so losing that much weight for him could be more problematic. Although it has been speculated that Steve Jobs was a vegan or vegetarian, apparently such was not the case (he was pescetarian, which is basically a vegetarian diet plus seafood). So post-surgical difficulties maintaining nutrition because of a special diet that might not have meshed well with Jobs’ new anatomy could have been the problem. Some other potential serious problems over the long term include glucose intolerance or even diabetes requiring insulin; malabsorption because of diminished production of pancreatic enzymes; delayed gastric emptying; the afferent loop syndrome; or the “dumping syndrome,” which is common after stomach resections and results from undigested food being “dumped” too fast into the proximal small intestine, which draws in fluid.

At the time, I speculated that perhaps it was afferent loop syndrome (ALS) that necessitated another operation. You’ve probably never heard of it unless you’ve been unfortunate enough to have it (or are a surgeon or gastroenterologist), but ALS is a potential complication after a certain type of gastrojejunostomy, which is when the stomach is connected to a loop of small bowel in an anastomosis. This leaves two “loops.” The efferent loop is the small bowel leading away from the anastomosis. The afferent loop is the loop proximal to the anastomosis, whose peristalsis runs towards the anastomosis. Bile and pancreatic juice dump into the afferent loop, as can be seen in the illustration above. If there is a mechanical problem with the afferent loop, it can result in symptoms soon after surgery or as long as many years later. That Jobs seems to be rather quickly looking worse nearly four years after his operation also suggests ALS.

There are two forms of the problem, acute and chronic. Acute ALS involves a high grade obstruction of the afferent limb, in which pancreatic juices and bile back up behind the obstruction under pressure, and is potentially life-threatening. The more common and chronic form is what can produce nutritional deficiencies over time. Usually, approximately 10-20 minutes to an hour after a meal, the patient will experience abdominal fullness and pain as the liver and pancreas pump bile and pancreatic juice into the partially obstructed afferent limb. These symptoms usually last from several minutes to an hour, although they occasionally last as long as several days. Pressure will build up and the obstruction will resolve by then, sometimes with vomiting. Prolonged ALS with stasis of digestive juices in the afferent limb can result in bacterial overgrowth of the digestive juices sitting there, fatty stools, diarrhea, and vitamin B-12 deficiency. The treatment is surgical, and if Jobs had ALS then his undergoing additional surgery made perfect sense.

Unfortunately, my speculation was wrong, as I found out a year later.

Pushing the limits of science-based medicine

The real bombshell regarding Steve Jobs’ health came in 2009. It’s a useful story to discuss because it demonstrates the limits of SBM and how sometimes they can be pushed in the cases of rare diseases for which there is little data. In early January, Jobs reported that he had been experiencing a “hormone imbalance” that needed treatment. In retrospect, even with all the secrecy, it should have been blazingly obvious that his insulinoma had recurred. All the signs were there, even through the veil of Apple secrecy, but somehow it was kept mostly out of the news until June, when the Wall Street Journal reported that Jobs had undergone a liver transplant:

In early January, Mr. Jobs said he had a hormone imbalance that was “relatively simple and straightforward” to treat. But about a week later, he announced that the issue was more complex than he had thought, and in a letter to employees he said he would be taking a leave and Mr. Cook would take over temporarily.

William Hawkins, a doctor specializing in pancreatic and gastrointestinal surgery at Washington University in St. Louis, Mo., said that the type of slow-growing pancreatic tumor Mr. Jobs had will commonly metastasize in another organ during a patient’s lifetime, and that the organ is usually the liver. “All total, 75% of patients are going to have the disease spread over the course of their life,” said Dr. Hawkins, who has not treated Mr. Jobs.

Getting a liver transplant to treat a metastasized neuroendocrine tumor is controversial because livers are scarce and the surgery’s efficacy as a cure hasn’t been proved, Dr. Hawkins added. He said that patients whose tumors have metastasized can live for as many as 10 years without any treatment so it is hard to determine how successful a transplant has been in curing the disease.

At the time, I looked into the issue, given that it had been a long time since I had finished my surgical oncology fellowship and I no longer took care of patients with neuroendocrine tumors, having specialized in breast cancer. In general, for neuroendocrine tumors metastastic to the liver, the first options to be considered are ablative options. These can include surgery, if the tumors are resectable, or ablation by various methods, such as radiofrequency ablation (RFA, or, as we like to say, “cooking the tumors”) or cryoablation (cryo, a.k.a. freezing the tumors). Surgery can be curative if the lesions are confined to a volume of liver that can be completely resected, and RFA is generally reserved when there are lesions in multiple lobes not amenable to surgical resection. For the consideration of a liver transplant, a patient must have multiple lesions in multiple lobes of the liver that are too numerous even to be cooked by RFA or frozen by cryo. Moreover, there can be no evidence of tumor anywhere other than in the liver. In addition, another indication is that symptoms must be such that they can’t be controlled by medical therapy. For an insulinoma, controlling the symptoms due to hypoglycemia can actually be quite difficult; so the type of tumor Jobs produced symptoms that are more difficult to palliate than the average neuroendocrine tumor.

So what are the results of liver transplant for neuroendocrine tumors? Because these tumors are so uncommon, there’s never going to be a randomized clinical trial. All that can be found in the literature consists of small case series or retrospective analyses.The kindest and most generous characterization that can be made is that that the evidence for treating neuroendocrine tumors metastatic to the liver with liver transplantation is mixed at best. A recent retrospective analysis of the UNOS database produced this survival curve (click to embiggen):

A picture’s worth a thousand words, and based on this curve alone Jobs had a little better a 50-50 chance of living as long as he did (almost two and a half years). Unfortunately, he fell out on the wrong side of those odds. Jobs’ case aside, the authors conclude:

Although surgical resection still should be considered the treatment of choice in patients with liver metastases from NETs, transplantation for unresectable disease is indicated in patients with stable disease without disseminated metastases. A national database should be developed to better understand predictors of outcomes in this patient population and to help produce and standardize selection criteria to obtain better outcomes. We believe it is time to carefully revise this indication.

Who could argue with more research? Jobs’ case is, however, an excellent example of the difficulties in deciding on a course of action when the evidence available is sparse. For instance, if he had progressive disease (and in retrospect it sounds as though he probably did), he probably should not have undergone transplantation, given that immunosuppression would probably facilitate the growth of microscopic tumor deposits and also given that it is possible to provide prolonged palliation by other means. Yet, to Jobs and his doctors at the time, the picture was probably anything but clear, other than that things were getting worse.

The war to claim Steve Jobs’ narrative

Since the death of Steve Jobs, there has been a struggle to claim his narrative as “evidence” to support a world view. On the one side, there are quacks using and abusing Jobs’ memory, as they’ve used and abused those of so many other dead celebrities to “prove” that “conventional medicine killed them.” Predictably, first out of the box is the despicable crank known as Mike Adams. Adams has made a not-so-savory name for himself for ghoulishly (and gleefully) taking advantage of the death of celebrities in order to blame “conventional” medicine for having killed them. It’s a depressing and predictable pattern that continued with Steve Jobs. Indeed, Adams produced an article on Steve Jobs’ death so quickly (within hours of the announcement of Jobs’ passing) that I have to wonder if he had already had it written and teed up, just waiting for Jobs to die. Whatever the case, Adams entitled his article, again predictably enough given his past history, Steve Jobs dead at 56, his life ended prematurely by chemotherapy and radiotherapy for cancer, which begins with a typical charge (from Adams) that Jobs’ gaunt appearance was due to chemotherapy, not the progression of his cancer, blaming his death on the “cancer industry” and claiming that it was “toxins” that caused his cancer and that “natural” treatments could have cured him.

Just yesterday, Joe Mercola chimed in, apparently managing to interview Nicholas Gonzalez right after Jobs’ death to produce this video:

Gonzalez, you may recall, is the originator of the “Gonzalez therapy” for pancreatic cancer, a therapy involving various juices, dietary manipulations, coffee enemas, and many, many supplements, as many as 150 pills per day. Also recall that his therapy, besides having no biological plausibility, has been convincingly demonstrated not to work.

The truly ironic thing, of course, is that Jobs lived a lifestyle very similar to the one that Adams touts as an all-purpose cancer preventative. As I mentioned before, Jobs was widely reported to be a vegan but was a was in fact a pescatarian. Jobs did not eat meat and the animal rights group PETA has paid homage to him after his death for being a vegetarian and sympathetic to animal rights causes. The point, of course, is that Steve Jobs ate a diet and lived a lifestyle far more similar to the kind that Adams touts as a cure-all or prevent-all for cancer than the “typical” fat- and meat-laden American diet that Adams lambastes. Upon his initial diagnosis, as we have seen, he eschewed surgery for nine months, trying to treat his cancer with a “special diet.” It’s not clear just what, exactly, this “special diet” was. Oddly enough, Gonzalez hints that he knows something:

He wanted to see an alternative. In fact when he was first diagnosed, he got some dietary program — again, he was very secretive of that — So I don’t exactly know what he did at that point. But through his acupuncturist, there was communication. He was getting acupuncture, and he was doing some alternative things as far as I know. This acupuncturist actually talked to me, discussing the situation. She was really anxious for him to come and see me. But he chose not to do that.

You know, I always respect the patients’ right to choose the therapy they want to choose, so I would never dispute that. The patients have to make the decisions based on what they want to do. But she was very adamant; in fact, she knew about all my works in the alternative world. He had seen alternative-type practitioners. She really wanted for him to come and see me. He chose not to do that. From my perspective, it was unfortunate, because he was such a gift to the world in terms of his inventions and genius in the past 30 years.

Yes, that’s Gonzalez claiming that he could have saved Jobs if only Jobs had listened to an acupuncturist.

For as much as the quacks are trying to claim that they could have cured Jobs if only they had given them the chance, there is, however, the chance of taking the opposite argument, namely that Jobs might have died because of his embrace of non-science-based treatments, too far in the other direction. Unfortunately, there is a skeptic who should really know better who did just that, using Steve Jobs’ death as evidence of the harm that alternative medicine can do. Now, given my reputation as someone who relentlessly applies the cudgel of reason, science, and critical thinking squarely to the back of the head of woo on a regular basis, you just might think that I would heartily approve of this line of argument. You’d be wrong, and not because I have any qualms whatsoever about appropriately blaming alternative medicine when someone pursues alternative medicine and ultimately dies. (I have, after all, done it myself on several occasions.) The key word is “appropriately,” and the reason that I’m not so hot on using Jobs’ death as a “negative anecdote” against “alternative” medicine is because I’m not so sure how appropriate doing so is in Jobs’ case. While Jobs certainly didn’t do himself any favors by waiting nine months to undergo definitive surgical therapy of his tumor, it’s very easy to overstate the potential harm that he did to himself by not immediately letting surgeons resect his tumor shortly after it was diagnosed eight years ago. Unfortunately, Brian Dunning does exactly that in his post A Lesson in Treating Illness (also posted over at Skepticblog):

I’m sad that today I’m adding a slide to one of my live presentations, adding Steve Jobs to the list of famous people who died treating terminal diseases with woo rather than with medicine.

Except that Jobs didn’t; at least, he didn’t for the most part. Aside from the initial nine months, Jobs, as far as we know, relied on exclusively on conventional therapy to treat his disease. In fact, he underwent the most invasive, cancer aggressive operation (the Whipple pancreaticoduodenectomy), which is one of the biggest, if not the biggest operation, that surgical oncologists do. Then, after his tumor recurred in his liver, he underwent the biggest, mot technically complex type transplant operation there is, a liver transplant. When his cancer recurred a second time earlier this year, Jobs was seen going to the Stanford Cancer Center in Palo Alto, California, looking frail and thin.

Moreover, the other “alternative” therapy reportedly pursued by Jobs in Switzerland was a therapy based on radiation therapy, you know, the kind of therapy known to the likes of Adams as “burning” the cancer. In any case, Jobs apparently traveled to the University Hospital of Basel in Switzerland to receive a form of “hormone-delivered radiotherapy.” For some reason this is being portrayed in the press as somehow “alternative.” In reality, from what I can tell, it’s science-based, but experimental. Basically, in this therapy, radioisotopes are linked to a peptide hormone, receptors for which are found on the tumor being treated. The hormone then binds to the receptors, bringing the radioisotope close enough to the tumor cells to deliver a high dose of radiation. This therapy is not “alternative”; although it’s not standard of care, it’s definitely science-based.

All of this leaves the sole remaining question regarding the issue of “alternative” medicine and cancer in the case of Steve Jobs as: Did Jobs significantly decrease his chance of surviving his cancer by waiting nine months to undergo surgery? It seems like a no-brainer, but it turns out that that’s actually a very tough question to answer. Certainly, it’s nowhere near as certain as Dunning tries to make it seem when he writes things like:

Eventually it became clear to all involved that his alternative therapy wasn’t working, and from then on, by all accounts, Steve aggressively threw money at the best that medical science could offer. But it was too late. He had a Whipple procedure. He had a liver transplant. And then he died, all too young.

One has to be very, very careful about making this sort of argument. For one thing, it could not have been apparent that it was “too late” back in 2004, when it became clear that Jobs’ dietary manipulations weren’t working. For another thing, we don’t know how large the tumor was, whether it progressed or simply failed to shrink over those nine months, and by how much it increased in size, if increase in size it did. Again, I hope that information will be revealed in the Jobs’ biography; such data would go a long way in clarifying just how much, if at all, Jobs might have compromised his chance for cure by delaying. Right now, we just don’t know enough to make even a good guesstimate. Based on what we do know now, the thing that has to be remembered is that neuroendocrine tumors of the pancreas tend for the most part to be fairly indolent, slow-growing tumors It’s very much overstating the case to write, as Dunning does:

As he dieted for nine months, the tumor progressed, and took him from the high end to the low end of the survival rate.

We don’t know that this was the case, and we certainly can’t say that for sure — or even with a great deal of certainty. Dunning is massively overstating the case in his eagerness to attack alternative medicine. This is a mistake. Again, I would certainly agree that Jobs did himself no favors by waiting. If I were his physician or the surgeon to whom he was referred, I would have done my best to talk him out of such a course of action, but I would do so more out of the uncertainty of not knowing how fast his tumor would progress. So, is it possible, even likely, that Jobs compromised his chances of survival? Yes. Is it definite that he did? No, it’s not, at least it’s not anywhere as definite as Dunning makes it sound. In fact, based on statistics alone, it’s unlikely that a mere nine months took Jobs “from the high end to the low end of the survival rate,” as Dunning puts it. That’s just not how insulinomas usually behave from a biological standpoint. They’re too indolent, and that’s not even taking into account issues of lead time bias and other confounding factors that would make comparisons of operating early versus operating later not as straightforward as one might think. Remember, Jobs’ tumor was probably what we call an “incidentaloma”; i.e., a finding picked up incidentally on a diagnostic test done for another reason. Consequently, it might not have caused symptoms for a long time. Or it might have already been causing symptoms, just symptoms that normally don’t warrant a CT scan. We don’t know; there isn’t enough information. Be that at it may, I have no doubt that Jobs might well have compromised his chances of survival by delaying, but it’s just not scientifically supportable to leap to the conclusion, as Dunning does, that he compromised his chances so much that “alternative medicine killed him.” What is known about Jobs’s case and insulinomas do not support such a conclusion; at worst they support a conclusion that Jobs might have decreased his chances somewhat.

If there’s one thing we’re learning increasingly about cancer, it’s that biology is king and queen, and that our ability to fight biology is depressingly limited. In retrospect, we can now tell that Jobs clearly had a tumor that was unusually aggressive for an insulinoma. Such tumors are usually pretty indolent and progress only slowly. Indeed, I’ve seen patients and known a friend of a friend who survived many years with metastatic neuroendocrine tumors with reasonable quality of life. Jobs was unfortunate in that he appears to have had an unusually aggressive form of the disease that might well have ultimately killed him no matter what. That’s not to say that we shouldn’t take into account his delay in treatment and wonder if it contributed to his ultimate demise. It very well might have, the key word being “might.” We don’t know that it did, which is one reason why we have to be very, very careful not to overstate the case and attribute his death as being definitely due to the delay in therapy due to his wanting to “go alternative.” Finally, Jobs’ case illustrates the difficulties with applying SBM to rare diseases. When a disease is as uncommon as insulinomas are, it’s very difficult for practitioners to know what the best course of action is, and that uncertainty can make for decisions that are seemingly bizarre or inexplicable but that, if you have all the information, are supportable based on what we currently know.

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I seem to be writing a lot about the urinary tract this month. Just coincidence, I assure you. As I slide into old age, medical issues that were once only of cursory interest for a young whippersnapper have increasing potential to be directly applicable to grumpy old geezers. Like benign prostatic hypertrophy (BPH). I am heading into an age where I may have to start paying attention to my prostate (not prostrate, as it is so often pronounced, although an infection of the former certainly can make you the latter), so articles that in former days I would have ignored, I read. JAMA this month has what should be the nail in the coffin of saw palmetto, demonstrating that the herb has no efficacy in the treatment of symptoms of BPH: Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial.

It demonstrated that compared to placebo, saw palmetto did nothing. There have been multiple studies in the past with the more or less the usual arc of clinical studies of CAM products: better designed trials showing decreasing efficacy, until excellent studies show no effect. There is the usual meta analysis or two, where all the suboptimal studies are lumped together, the authors bemoan the quality of the data, and proceed to draw conclusions from the garbage anyway. GIGO.

The NEJM study from 2006 demonstrated that saw palmetto was no better than placebo but it was suggested that perhaps the dose of saw palmetto was not high enough or that the patients were not treated long enough to demonstrate an effect, and the JAMA study hoped to remedy that defect.There is, as is often the case, no good reason to suspect that saw palmetto would benefit or harm the prostate. Like many herbal preparations, it had widespread uses back in the day, when I had an onion tied to my belt, which was the style at the time. You couldn’t get white onions, because of the war. The only thing you could get was those big yellow ones.., but I digress:

“It is also an expectorant, and controls irritation of mucous tissues. It has proved useful in irritative cough, chronic bronchial coughs, whooping-cough, laryngitis, acute and chronic, acute catarrh, asthma, tubercular laryngitis, and in the cough of phthisis pulmonalis. Upon the digestive organs it acts kindly, improving the appetite, digestion, and assimilation. However, its most pronounced effects appear to be those exerted upon the urino-genital tracts of both male and female, and upon all the organs concerned in reproduction. It is said to enlarge wasted organs, as the breasts, ovaries, and testicles, while the paradoxical claim is also made that it reduces hypertrophy of the prostate. Possibly this may be explained by claiming that it tends toward the production of a normal condition, reducing parts when unhealthily enlarged, and increasing them when atrophied.”

At the turn of century Edwin M Hale, MD and homeopath, wrote a treatise on the topic, extolling its benefits on the prostate and other organs. You will be happy to know that if you have testicular atrophy from being an old masturbator, saw palmetto will help. For no good reason I can find, it became popular only for BPH. As best I can determine from the internet, there was a natural medicine fad in the early 1900’s, and saw palmetto became part of the fad. No clinical trials were responsible for the use. And, like acupuncture and homeopathy, there are many explanations for an efficacy that does not exist.

The JAMA study followed 369 men for 72 weeks. They received placebo or saw palmetto twice a day, and at weeks 24 and 48 the dose of each was increased.

They were followed for subjective complaints with the AUASI score, which is a 7 question self administered questionnaire:

Well validated as a tool for BPH symptoms, it relies overmuch on memory and is subject to wishful thinking on the part of the test taker. I doubt I could ever accurately remember my urinary patterns over the prior month without writing it down.

There were also objective endpoints like peak urine flow, PSA levels, and post void residual. Makes me wonder again what they want done when the radio advertisement says ‘Void were prohibited by law.’ Would saw palmetto make that easier? When it came to the subjective measurements, there was a slight, and similar, improvements in both groups. Objective, anatomic and physiologic endpoints were not affected. No surprise. So much for the powerful placebo.

Adverse effects were the same in both groups, with the only significant difference that the saw palmetto group had more physical injury and trauma. Was this the dreaded nocebo effect, or the random badness that occurs as a result of life? Probably the latter.

Based on the JAMA and NEJM trials, it is reasonable to conclude that saw palmetto has no efficacy in the treatment of symptoms due to BPH.

More interesting is what this article says about the so called placebo effect. This is yet another article that demonstrates that for hard endpoints, altering abnormal physiology or anatomy, placebo does nothing. I bet if we did brain scans of these patients they would show changes when the patient took the medications, and to that I would yawn. Do anything to anyone, give a placebo, tickle their feet, there will be changes in the brain. And while in some studies, increasing placebo amounts and frequency leads to increasing effects, in this study an increase in placebo dose led to no improvement in subjective outcomes.

More real world data to suggest that there are no real placebo effects.

Of course, I have bias. I have spent 30 years in acute care hospitals. My patients have derangements of anatomy and physiology that, if not corrected or at least ameliorated, lead to death or permanent morbidity. Placebo isn’t going to cure endocarditis, stop a gastric ulcer bleed, or reverse a stroke. And even if the patient feels better from the therapeutic relationship, if the anatomic/pathophysiologic abnormalities continue unabated, the patient is toast.

I am not even certain it can be said that placebos cure gastric ulcers. There is little on the natural history of ulcers in the flexible endoscopy age. The only reference I could find suggests that patients who have ulcers found with x-ray screening (not a reliable way to diagnose ulcers and probably under-represented the incidence) and who are not treated had a 24% cure rate at 6 months and a 29% relapse rate at 24 months. Most of the placebo trials followed patients around 4 weeks and had a higher cure rate in the placebo wing than seen in the natural history report, but the two are not directly comparable. Given the propensity of untreated ulcers to come and go and the unreliability of symptoms for diagnosis, unless there was a study that had a treatment, a placebo, and a no intervention arm, I do not think it is reasonable to conclude that placebos ‘cure’ ulcers. Especially given the NEJM review that suggested that placebo is usually no more effective than a no treatment/waiting arm.

Perhaps it is me. I do have some intellectual blind spots, like the anthropic principal. Every time I come across it in a cosmology book, I think that it is inane. I lack the imagination, or perhaps I am not stoned enough, to recognize its significance. So too with the placebo effect.

Placebo effects are probably more like quantum mechanics. The single slit experiment gives key insights into the fundamental nature of reality, but in the macroscopic world of day to day life my electrons move about just fine to heat my house and run my computer. No need to worry about probability functions, I can throw potatoes at a slit all day and never see a interference pattern. So too with the placebo effect. Most of the practical effect is lost in the noise of the complexity of illness, especially in the acute care hospital where I spend most of my time.

As Harriet quotes Dr. Benedetti

the take-home message for clinicians, for physicians, for all health professionals is that their words, behaviors, attitudes are very important, and move a lot of molecules in the patient’s brain. So, what they say, what they do in routine clinical practice is very, very important, because the brain of the patient changes sometimes… there is a reduction in anxiety; but we know that there is a real change…in the patient’s brain which is due to… the ‘ritual of the therapeutic act.’

I do not disagree with that. I consciously try to accentuate just those interactions with every patient, because I know my job as a physician is more than ‘Me find bug, Me kill bug. Me go home’. But I do not think it is important for modifying any disease process I am involved with. Grooming each other has salubrious effects in monkeys, and as best I can tell, the placebo is no more than evolutionarily advanced nit picking.

Large swaths of the world rely on native healers and the only tool in their armamentarium is the “ritual of the therapeutic act.” And across the world and throughout time, people have suffered and died in droves. You may argue that is not a fair comparison, people suffered from poor hygiene, no vaccines, malnutrition and no health infrastructure. But the US has a group whose health care is only placebo, relying entirely on the ritual of the therapeutic act, and despite being surrounded by the benefits of western societal infrastructure, they die faster and younger: Christian Scientists.

At the end of the day, the practice of medicine is practical endeavor. I am a builder, not an architect. I have to try to make my patients better objectively and subjectively, and the placebo is a tool that has little utility in my toolbox. When my prostate grows to the size of a tennis ball, I am going to go looking for a therapy that will shrink it, not fool me into thinking I can write my name in the snow a little better.

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Acupuncture is typically depicted as sticking needles at various points on the body prescribed (inconsistently, it turns out) by charts indicating purported “meridians” through which “qi” flows in the human, or animal , body. However, from one of the many SBM posts on acupuncture , this one by Dr. Novella , we in fact know that:

the consensus of the best clinical studies on acupuncture show that there is no specific effect of sticking needles into acupuncture points. Choosing random points works just as well, as does poking the skin with toothpicks rather than penetrating the skin with a needle to elicit the alleged “de qi”. The most parsimonious interpretation of the evidence is that the needles (i.e. acupuncture itself) are superfluous — any perceived benefit comes from the therapeutic interaction. This has been directly studied, and the evidence suggests that the way to maximize the subjective effects from the ritual of acupuncture is to enhance the interaction with the practitioner, and has nothing to do with the acupuncture itself. Acupuncture is a clear example of selling a specific procedure based entirely on non-specific effects from the therapeutic interaction — a good bedside manner and some hopeful encouragement.”

Unfortunately, those who draft state legislation do not read SBM. They should. If they did, they wouldn’t be enacting acupuncture practice acts. But they do.

Through the magic of legislative alchemy, acupuncture or, in some cases, “oriental medicine,” is a licensed health care profession in 43 states. Like naturopaths, acupuncturists attempted to expand their geographic range in 2011 and, like chiropractors as well, tried to broaden their scope of practice to include methods and treatments far from their original tradition, wherever that may lie.

Kansas does not become the 44th state

Kansas does not license acupuncturists as a separate “healing art,”although, by statute, both naturopaths and veterinarians can employ acupuncture in their practices. In 2011, the “acupuncture and oriental medicine practice act” was introduced in the state Senate but never made it out of the Public Health and Welfare Committee.

Although it failed, it is worth reviewing for those unfamiliar with acupuncture practice acts as it demonstrates the startlingly broad scope of practice typically granted acupuncturists and “oriental medicine” practitioners by state law. It is as well a perfect example of legislative alchemy in its incorporation of sheer nonsense.

As with recent attempts by chiropractors to sound less chiropractic , acupuncturists are apparently trying to camouflage the more psuedoscientific- sounding concepts by re-casting them in what we might call faux biomedical language. Thus, nowhere in the Kansas legislation will you find any reference to “qi” or “meridians.” No, here acupuncture is

a form of health care that is based on a theory of energetic physiology that describes and explains the interrelationship of bodily organs or functions with an associated acupuncture point or combination of points that are stimulated in order to restore the normal function of the bodily organ or function.”

Thus, the “practice of acupuncture” is

the use of needles or of oriental medicine therapies for the purpose of normalizing energetic physiological functions including pain control and for the promotion, maintenance and restoration of health.”

“Qi” and “meridian” are out. “Energetic physiological functions” are in. And needles are not the only way to “normalize” these “energetic physiological functions.” Not by a long shot.

Acupuncturists would also have at their disposal “oriental medicine therapies.” And what exactly is “oriental medicine?” According to this proposed legislation, “oriental medicine”

means the distinct system of health care that uses health techniques of oriental medicine, both traditional and modern, to diagnose, evaluate, examine, manage and treat for the prevention, cure or correction of disease, illness, injury, pain or other physical or mental condition by controlling and regulating the flow and balance of energy, form and function to restore, promote and maintain health.”

So, “oriental medicine” is health care that uses “oriental medicine.” Got it? I suppose the fact that it must achieve its purpose by “controlling and regulating the flow and balance of energy, form and function” is somewhat of an explanation. I do not know, for there is no clue in the proposed statutory language, whether said “regulating the flow and balance of energy” etc. is the same thing as “normalizing energetic physiological functions.” Whatever that means.

In this vein of “daffy definitions,” we also learn that:

• “biofeedback device” is “an instrument that is used to detect and amplify internal physiological processes and mental functioning.”
• “herbal and animal-based substances” includes substances of “animal, vegetable or mineral origin.”(emphasis added) (I suppose the draftsman of this legislation missed that day in biology, or missed biology altogether.)
• “Nutritional supplement means a nutritional substance, including a concentrate or extract of such a substance.” (That’s it — the entire definition.)

Under the proposed statute, the “practice of acupuncture includes, but is not limited to:”

dietary and nutritional counseling “based on traditional [but not "modern", apparently] Chinese medical principles”

recommendation, administration or dispensing of food, vitamins, minerals, enzymes, homeopathic preparations, amino acids or nutritional supplements (see above for definition).

So, homeopathy, supplements, diet, amino acids, vitamins, minerals, enzymes and biofeedback devices were all to become part of acupuncture practice under the new law. Apparently what acupuncturists, like chiropractors, really want to be is naturopaths.

Expanding scope of practice

Acupuncturists in Connecticut, where they are already licensed, were successful in expanding their practice by convincing the legislature to abandon any control over what they do as long as their practices are “consistent with accepted standards within the acupuncture and Oriental medicine profession.”

This was accomplished in a single section of a 98-section public health bill governing such diverse topics as regulation of day care, treatment of STDs, recording of vital statistics, and needle exchange programs. The term “sneaking it in” comes to mind.

Connecticut had already modernized, if you will, acupuncture by eschewing the old-fashioned terms “qi” and “meridians” for “the theory of physiological interrelationship of body organs with an associated point or combination of points for diseases, disorders and dysfunctions of the body.” The new practice act, however, abandons that definition for “modulation and restoration of normal function in and between the body’s energetic and organ systems and biomechanical, metabolic and circulation functions using stimulation of selected points.” Whether this is a new “theory” or simply a restatement of the old “theory” is not disclosed.

In any event, Connecticut acupuncturists are no longer limited to “needles, heat, pressure or electrical stimulation” of said points. Now any “method” is ok as long as it complies with the aforementioned “standards” of the “acupuncture and Oriental medicine profession.”

Also added as means for achieving “promotion and maintenance [as opposed to “modulation and restoration”] of normal function in the body’s energetic and organ system and biochemical, metabolic and circulation functions” are “Oriental dietary principles,” including (of course!) “supplements” and “other practices . . . consistent with the recognized standards of the . . . profession and accepted by the National Certification Commission for Acupuncture and Oriental Medicine.”

Acupuncturists can now also perform “assessment of body function, development of a comprehensive treatment plan and evaluation of treatment outcomes according to acupuncture and Oriental medicine theory.”

Putting it all together, the Connecticut acupuncturist will now be able to assess the body’s energetic system, treat the energetic system with any method consistent with professional standards, and know when the energetic system is modulated/restored/promoted/maintained through assessment of treatment outcomes. An amazing achievement considering that no research has ever demonstrated that this “energetic system” exists or what its properties might be.

 The acupuncturist as naturopath

In addition to their try for licensing in Kansas, and success at expanding their scope of practice in Connecticut, acupuncturists attempted to become naturopaths in other states where they are already licensed. To date, success has eluded them.

In Ohio, a bill would have added a new type of practice — “Oriental Medicine” — separate from acupuncture, while at the same time increasing the scope of practice for acupuncturists. Acupuncturists would be allowed to use “supplemental techniques” including “the use of traditional and modern oriental therapeutics [the scope of which are not defined], counseling [including] the provision of information regarding lifestyle modifications and the therapeutic use of foods and supplements including homeopathics, gladulars, vitamins, and minerals.”

“Oriental medicine” practice, on the other hand, is defined as “a form of health care in which acupuncture is performed with or without the use of herbal therapy” which is not the same as “supplemental techniques” (see above). Once again demonstrating that one does not need to have taken biology to draft licensed health care provider legislation, “herbal therapy” is defined as “the use of herbs, vitamins, minerals, organ extracts, homeopathics or physiological materials for energetic or physiologic therapy.”

New York Senate and Assembly bills would expand “the profession of acupuncture” to allow “recommendation of traditional remedies and supplements including, but not limited to, the recommendation of diet, herbs and natural products, and their preparation in accordance with traditional and modern practices of modern East Asian or Oriental (Chinese, Korean or Japanese) medical theory.” What! No homeopathy?

Acupuncture for drug addiction

In Massachusetts, a bill would expand the scope of acupuncture practice to treat drug addiction via “Acupuncture Injection Therapy” defined as “the injection of herbs, homeopathic, and other nutritional supplements in the form of sterile substances into acupuncture points by means of hypodermic needles but not intravenous therapy.” The purpose of this is to “help prevent addiction to prescription drugs and prevent and reduce drug abuse; to promote, maintain, and restore health; for pain management and palliative care; and for acupuncture anesthesia.” This is so obviously dangerous that snark escapes me. The bill has not passed, although the Massachusetts legislature has not adjourned for the year.

“Acupuncture Injection Therapy” is not the only way acupuncture is used to treat substance abuse. In Colorado, licensed acupuncturists already use “five point NADA auricular acupuncture” which, as a bill summary explains, “is acupuncture done on the ear that is often used to treat substance abuse, mental health and behavioral health disorders.” “NADA” is the “National Acupuncture Detoxification Association.”

Apparently, other health care providers want to get in on the act, so proposed legislation would allow chiropractors, physicians, physician assistants, nurses, mental health professionals, and psychiatric technicians to perform this “five point NADA auricular acupuncture” but only if, as further explained in the summary, “they have successfully completed the proper training.” This bill actually made it to the Colorado House floor, where it failed to pass.

 New Mexico

Faithful SBM readers will be wondering by now, “what about New Mexico, the state where anyone can practice medicine?” And they won’t be disappointed. There was, of course, a bill introduced in New Mexico to expand the acupuncturists’ scope of practice.

In New Mexico, as you might guess, acupuncturists already have limited prescriptive authority. Too limited, in their opinion.

First, they attempted to eliminate the requirement that prescription of “devices” be limited to those “necessary in the practice of oriental medicine.” As for drugs and their mode of administration, acupuncturists already had a formulary in the current practice act, but apparently didn’t like it. So, as did the New Mexico chiropractors, they tried to change it. It would have specifically included the following, although whether the acupuncturists could already prescribe and administer some of these under the current statute is unclear: subcutaneous and intramuscular epinephrine, injectable vitamin B-12, intradermal and subcutaneous injection of homeopathics, dextrose, minerals, sarapin and vitamins, and IV administration of water-soluble vitamins and minerals.

While, under the current statute, acupuncturists can prescribe “bioidentical hormones” they would be able to prescribe under the proposed expansion “topical estradiol, estriol, progesterone, testosterone and desiccated thyroid,” but only if the acupuncturist had “a signed collaborative practice agreement” with an M.D. or D.O. Thus, as with chiropractors and naturopaths who want to prescribe real drugs, adult supervision would be required. The bill died in committee.  Even New Mexico has its standards.

Sticking needles in healthy people

As noted in the Introduction, research discloses that it doesn’t matter where you stick the needle in acupuncture. A bill introduced in the Oregon legislature was refreshingly honest about that fact. The bill, which died in committee, would have changed the statutory definition of acupuncture, currently “an Oriental health care practice used to promote health and to treat neurological, organic or functional disorders by the stimulation of specific points on the surface of the body by the insertion of needles.” “Oriental” would have been removed, as would have “specific points,” which simply became “points in and on the body.” In other words: stick it anywhere, it’s all the same.

As also noted, acupuncture doesn’t work. This makes it perfect for treating someone who isn’t sick, as a Pennsylvania bill — most certainly unintentionally — acknowledged. Under Pennsylvania law, acupuncturists can treat “a person’s condition” without the condition being diagnosed by a physician, dentist or podiatrist for 60 days. After that time, the treatment may continue only if the person “obtained a diagnosis of the treated condition” by a physician, dentist or podiatrist. A proposed amendment to this law would make these limitations inapplicable “if a person does not present any symptoms of a condition.”

It’s really the ideal “CAM” legislation — ineffective treatments for people who are not ill — and it may become state law. Both the House and Senate versions of this bill have made it to the floor of the Pennsylvania legislature, which meets year-round.

Conclusion

As I’ve said before, no person should be subjected to scientifically implausible diagnostic methods and treatments. States should be working to eliminate such practices, not giving out licenses to perpetuate them.

Which brings me to “The Cure,” anti-sCAM legislation I’ll be proposing in a future post. Stay tuned.

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While we frequently on SBM target the worst abuses of science in medicine, it’s important to recognize that doing rigorous science is complex and mainstream scientists often fall short of the ideal. In fact, one of the advantages of exploring pseudoscience in medicine is developing a sensitive detector for errors in logic, method, and analysis. Many of the errors we point out in so-called “alternative” medicine also crop up elsewhere in medicine – although usually to a much less degree.

It is not uncommon, for example, for a paper to fail to adjust for multiple analysis – if you compare many variables you have to take that into consideration when doing the statistical analysis otherwise the probability of a chance correlation will be increased.

I discussed just yesterday on NeuroLogica the misapplication of meta-analysis – in this case to the question of whether or not CCSVI correlates with multiple sclerosis. I find this very common in the literature, essentially a failure to appreciate the limits of this particular analysis tool.

Another example comes recently from the journal Nature Neuroscience (an article I learned about from Ben Goldacre over at the Bad Science blog). Erroneous analyses of interactions in neuroscience: a problem of significance investigates the frequency of a subtle but important statistical error in high profile neuroscience journals.

The authors, Sander Nieuwenhuis, Birte U Forstmann, and Eric-Jan Wagenmakers, report:

We reviewed 513 behavioral, systems and cognitive neuroscience articles in five top-ranking journals (Science, Nature, Nature Neuroscience, Neuron and The Journal of Neuroscience) and found that 78 used the correct procedure and 79 used the incorrect procedure. An additional analysis suggests that incorrect analyses of interactions are even more common in cellular and molecular neuroscience.

The incorrect procedure is this – looking at the effects of an intervention to see if they are statistically significant when compared to a no-intervention group (whether it is rats, cells, or people). Then comparing a placebo intervention to the no-intervention group to see if it has a statistically significant effect. Then comparing the results. This seems superficially legitimate, but it isn’t.

For example, if the intervention produces a barely statistically significant effect, and the placebo produces a barely not statistically significant effect, the authors might still conclude that the intervention is statistically significantly superior to placebo. However, the proper comparison is to directly compare the differences to see if the difference of difference is itself statistically significant (which it likely won’t be in this example).

This is standard procedure, for example, in placebo-controlled medical trials – the treatment group is compared to the placebo group. But what more than half of the researchers were doing in the articles reviewed is to compare both groups to a no-intervention group but not comparing them to each other. This has the effect of creating the illusion of a statistically significant difference where none exists, or to create a false positive type of error (erroneously rejecting the null hypothesis).

The frequency of this error is huge, and there is no reason to believe that it is unique to neuroscience research or more common in neuroscience than in other areas of research.

I find this article to be very important, and I thought it deserved more play than it seems to be getting. Keeping to the highest standards of scientific rigor is critical in biomedical research. The authors do an important service in pointing out this error, and researchers, editors, and peer reviewers should take note. This should, in fact, be part of a check list that journal editors employ to ensure that submitted research uses legitimate methods. (And yes, this is a deliberate reference to The Checklist Manifesto – a powerful method for minimizing error.)

I would also point out that one of the authors on this article, Eric-Jan Wagenmakers, was the lead author on an interesting paper analyzing the psi research of Daryl Bem. (You can also listen to a very interesting interview I did with Wagenmakers on my podcast here.) To me this is an example of how it pays for mainstream scientists to pay attention to fringe science – not because the subject of the research itself is plausible or interesting, but because they often provide excellent examples of pathological science. Examining pathological science is a great way to learn what makes legitimate science legitimate, and also gives one a greater ability to detect logical and statistical errors in mainstream science.

What the Nieuwenhuis et.al. paper shows is that more scientists should be availing themselves of the learning opportunity afforded by analyzing pseudoscience.

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Science-based medicine rests on twin pillars that are utterly essential to the development of treatments that are safe and efficacious. Both of these pillars depend on science, but in different ways. The first of these is, of course, the basic science that provides the hypotheses to test about the mechanisms behind the diseases and malfunctions that plague the human body. This basic science suggests ways of either correcting or alleviating these malfunctions in order to alleviate symptoms and prevent morbidity and mortality and how to improve health to increase quality and quantity of life. Another critical aspect of basic science is that it also provides scientists with an estimate of the plausibility of various proposed interventions, treatments and cures designed to treat disease and improve health. For example, if a proposed remedy relies upon ideas that do not jibe with some of the most well-established laws in science, such as homeopathy, the concepts behind which violate multiple laws of physics and chemistry, it’s a very safe bet that that particular treatment will not work and that we should test something else. Of course, the raison d’être of this blog derives from the unfortunate fact that in today’s medicine this is not the case and we are wasting incredible amounts of time, money, and lost opportunities in order to pursue the scientific equivalent of fairy dust as though it represented a promising breakthrough that will save medicine, even though much of it is based on prescientific thinking and mysticism. Examples include homeopathy, reiki, therapeutic touch, acupuncture, and much of traditional Chinese medicine and Ayurveda, all of which have managed to attach themselves to medical academia like kudzu.

Of course, basic science alone is not enough. Humans are incredibly complex organisms, and what we consider to be an adequate understanding of disease won’t always result in an efficacious treatment, no matter how good the science is. Note that this is not the same thing as saying that utter implausibility from a scientific basis (as is the case with homeopathy) doesn’t mean a treatment won’t work. When a proposed treatment relies on claiming “memory” for water that doesn’t exist or postulates the existence of a “life energy” that no scientific instrument can detect and the ability to manipulate that life energy that no scientist can prove, it’s a pretty safe bet that that treatment is a pair of fetid dingo’s kidneys. Outside of these sorts of cases, though, clinical trials and epidemiological studies are the second pillar of science-based medicine, in particular clinical trials, which is where the “rubber hits the road,” so to speak. In clinical trials, we take observations from the laboratory that have led to treatments and test them in humans. The idea is to test for both safety and efficacy and then to begin to figure out which patients are most likely to benefit from the new treatment.

Over the last 50 or 60 years, for all its flaws (and what system devised by humans doesn’t have flaws?) it’s been a highly effective system. When it works well, physicians take observations from the clinic, go to the laboratory, where basic scientists and physicians try to figure out what’s going on to explain a particular observation and then develop an intervention, after which that intervention, be it a drug, procedure, or other treatment, is taken back to the clinic to test. In practice, this process can be very messy, as biases such as publication bias, selection bias, and other confounding factors can at times mislead. Money can corrupt the process as well, given that clinical trials are the final common pathway to the approval of new drugs by the Food and Drug Administration and the hundreds of millions of dollars it costs pharmaceutical companies to bring a single drug from bench to final phase III clinical trials in the hopes of recouping that investment and making large profits besides. Despite all that, no one has as yet been able to propose a better process.

That’s not to say that periodically there aren’t proposals to radically reinvent the clinical trials process. Certainly, I can sympathize to a point; being involved in clinical trials myself, I understand how even a relatively small clinical trial involves an enormous amount of time, money, and regulatory hurdles to jump over. I’ve never personally run a large phase III trial (although I hope to some day); so I can only know what that would be like from my interactions with colleagues who have. In any case, it’s the onerous nature of the current clinical trial system that has led to a recent editorial published in Science by Andrew Grove, former Chief Executive Officer of Intel Corporation and a patient advocate at the University of California, San Francisco, entitled, appropriately enough, Rethinking Clinical Trials. From the article, it’s obvious that Groves is not a scientist, but that doesn’t mean he isn’t worth listening to—to a point. Unfortunately, his proposed solution is unlikely to work, even though he does have a grasp of the problem:

The biomedical industry spends over $50 billion per year on research and development and produces some 20 new drugs. One reason for this disappointing output is the byzantine U.S. clinical trial system that requires large numbers of patients. Half of all trials are delayed, 80 to 90% of them because of a shortage of trial participants. Patient limitations also cause large and unpredicted expenses to pharmaceutical and biotech companies as they are forced to tread water. As the industry moves toward biologics and personalized medicine, this limitation will become even greater. A breakthrough in regulation is needed to create a system that does more with fewer patients.

Groves does have a point in that the clinical trial system in this country has indeed become quite expensive and unwieldy. He’s also correct that the evolution towards “personalized medicine” will exacerbate the problem. The reason is that, as we check more and more biomarkers or genetic markers to guide therapy, we will decrease the number of patients falling into each category requiring a certain drug, in essence, slicing and dicing the patient population into ever smaller slivers, each of whose treatment will be different. Sorting all this out will be quite difficult. Unfortunately, Groves approaches the problem from the wrong perspective in that it’s clear he has little feeling for how science should be applied to medicine, as will become clear by his analogy:

The current clinical trial system in the United States is more than 50 years old. Its architecture was conceived when electronic manipulation of data was limited, slow, and expensive. Since then, network and connectivity costs have declined ten thousand–fold, data storage costs over a million-fold, and computation costs by an even larger factor. Today, complex and powerful applications like electronic commerce are deployed on a large scale. Amazon.com is a good example. A large database of customers and products form the kernel of its operation. A customer’s characteristics (like buying history and preferences) are observed and stored. Customers can be grouped and the buying behavior of any individual or group can be compared with corresponding behavior of others. Amazon can also track how a group or an individual responds to an outside action (such as advertising).

Yes, you heard that right. Groves thinks that doing science is enough like cataloging customer orders, preferences, and history the way Amazon.com does. So what’s his suggestion? In essence, Groves is proposing what is commonly known a “pragmatic trial” but on megadoses of steroids, all using computers to figure out what’s going on:

We might conceptualize an “e-trial” system along similar lines. Drug safety would continue to be ensured by the U.S. Food and Drug Administration. While safety-focused Phase I trials would continue under their jurisdiction, establishing efficacy would no longer be under their purview. Once safety is proven, patients could access the medicine in question through qualified physicians. Patients’ responses to a drug would be stored in a database, along with their medical histories. Patient identity would be protected by biometric identifiers, and the database would be open to qualified medical researchers as a “commons.” The response of any patient or group of patients to a drug or treatment would be tracked and compared to those of others in the database who were treated in a different manner or not at all. These comparisons would provide insights into the factors that determine real-life efficacy: how individuals or subgroups respond to the drug. This would liberate drugs from the tyranny of the averages that characterize trial information today. The technology would facilitate such comparisons at incredible speeds and could quickly highlight negative results. As the patient population in the database grows and time passes, analysis of the data would also provide the information needed to conduct postmarketing studies and comparative effectiveness research.

I found out about Andy Groves’ article from Derek Lowe, who didn’t think that much of it but didn’t dismiss it altogether. I tend to agree, although I suspect I’ll end up being a little bit harder on it than Derek is. And it’s not an altogether crazy idea. It’s not even necessarily that bad an idea, except that Groves clearly doesn’t understand clinical trials, and you have to understand clinical trials before you can apply technology to it. For example, Groves seems to labor under the delusion that phase I trials prove safety of a new medication. That is a gross misunderstanding of the purpose of the phase I trial. Yes, checking for safety is part of what a phase I trial does, but a phase I trial doesn’t “prove safety.” What a phase I trial does is to rule out any really major side effects or toxicities that are common (remember, phase I trials usually only have around 20 to 100 participants, too small a number to catch uncommon adverse events), study pharmacokinetics (how the drug level varies with dose and how it’s metabolized), and establish both a maximal tolerated dose and a dosing interval. This last purpose is usually achieved using a technique as dose escalation Often phase I trials are performed using healthy volunteers, although in my specialty (cancer) that’s rarely the case. In any case, a better way of describing the purpose of a phase I was summed up by Freedman, “[T]he reason for conducting the trial is to discover the point at which a compound is too poisonous to administer.” That’s exactly what I meant by “maximal tolerated dose.”

Yes, that is the purpose of a phase I “first in humans” clinical trial. It’s absolutely necessary, too.

Here’s the problem with Groves’ idea. What he is basically proposing is to do, in essence, a whole bunch of “N of 1″ trials, each patient being a clinical trial in and of himself or herself. Then, through the magic of computer technology, he seems to be suggesting that we take all these “N of 1″ trials and try to do a meta-analysis of them. Here, we have a case where more does not necessarily mean better. What will result are data that are ridiculously heterogeneous—possibly unanalyzably so. As Derek Lowe points out, one of the most difficult aspects of clinical trial design is to standardize the treatment, to make sure that patients across multiple clinical trial sites are actually being treated and followed in the same way. Under Groves’ concept, heterogeneity is a feature, not a bug. However, it is not this aspect that bothers me so much about this proposal. Rather, it’s Groves’ dismissive comment about “liberating” clinical trials from the “tyranny of averages.” As if averages are a bad thing! That “tyranny of averages” is what makes sure that the patients being enrolled in a clinical trial are comparable to each other. Without relatively strict inclusion criteria in early phase II trials, the most likely thing that would happen if Groves’ proposal were adopted is that any signal would be drowned out by all the noise due to the heterogeneity of the patients and the data derived from each “N of 1″ trial.

Perhaps the biggest practical problem with Groves’ idea is how patients will be selected for therapies. Notice how Groves says that “once safety is proven, patients could access the medicine in question through qualified physicians.” There’s another problem with this concept other than the lack of recognition of the fact that phase I trials don’t “prove safety,” and that’s the issue of who decides which patients will take the drug, and basically it appears to me that what Groves is proposing is that any physician can take any drug that has passed phase I testing and offer it to any patient. As much as Groves prattles on about “real world” efficacy, this is a real world recipe for disaster. First, phase I trials do not demonstrate efficacy; they only evaluate safety and toxicity. Consequently, it is difficult (for me, at least) to imagine how physicians could ethically administer drugs whose efficacy has not been demonstrated or, more importantly, how they could know for which patients these new drugs would be appropriate. (Short answer: They can’t.”) It’s difficult enough to maintain clinical equipoise.

Indeed, one huge unspokean (and unsupported) assumption is that allowing unfettered access to experimental drugs that have passed phase I trials would help more people than it would hurt. In actuality, because phase I trials only identify acute toxicities and do not identify adverse reactions that occur with longer use, physicians administering these drugs would be flying almost blind. The potential for harm is enormous, particularly when it is powerful chemotherapeutic agents that are being given. It is far more likely that widespread use of unapproved substances would harm far more patients than it would help. Indeed, at the level of the individual patient, trying such drugs is more likely to harm than help. If there’s one thing worse than dying of cancer, it’s making one’s last days shorter and more miserable with toxicities from unapproved drugs or, even worse still, paying big bucks to do so.

Yet, somehow Groves seems not to have considered this possibility.

Perhaps the most problematic aspect of Groves’ entire proposal, though, is the very reason why we do clinical trials, namely to answer the question, “Does the drug work?” In a system such as that proposed by Groves, how, exactly, would we figure out whether a drug works or not? What would be the endpoint? What result would tell us that the drug is doing what it is intended to do? For example, in the case of cancer chemotherapy drugs, the purpose of the drug is to prolong survival. Figuring out if a new drug did that is difficult enough in the current system of clinical trials. Indeed, we already know from the example of Avastin in breast cancer that teasing out whether an improvement in disease-free survival translates into an improvement in overall survival. Under Groves’ proposal, it would be well nigh impossible. Groves seems to be arguing that, if we just keep track of enough variables and possible confounding factors, everything will shake out due to the wonder of modern computerized “e-commerce”-style tracking applied to patients. Maybe that’s possible. Maybe (and more likely) such a system will result in an uninterpretable mass of data from which extracting meaningful correlations will be at best problematic, at worst impossible. Even if it does work, then what is the endpoint of a clinical trial? When can investigators declare that they’ve accrued enough patients.

Remember how I referred to Groves’ proposal as being in essence replacing the current clinical trial system with that of “pragmatic trials”? We’ve been very critical here at SBM of the use and abuse of pragmatic trials by proponents of quackademic medicine. In fact, more than anything else, what Groves is proposing comes across to me as a high tech version of the very same pragmatic trials that acupuncturists are agitating for. There are no controls, which means that placebo responses will go uncorrected for. There are a plethora of variables and potential confounding factors, which would also be unaccounted for.

Don’t get me wrong. I’m not dismissing Groves’ idea; I’m merely pointing out that he has an incredibly simplistic view of how clinical trials operate and what evidence must be obtained before it’s reasonable to conclude that a new treatment “works” for a particular illness. Basically, spurred on by his own personal battles with prostate cancer and Parkinson’s disease, he has had a late life conversion to patient advocate. There’s nothing wrong with that and much to be admired, but unfortunately Groves seems to think that his knowledge of the computer and semiconductor industry is easily transferable to the pharmaceutical industry. It’s not for nothing that four years ago Derek Lowe also referred to Groves as Rich, Famous, Smart, and Wrong. Groves expresses frustration at the slow pace of research into Parkinson’s disease and other diseases. Fair enough. If I had a relentless degenerative neurological condition that would slowly rob me of my ability to function (and, in particular, to do surgery and write), I’d be frustrated too. Unfortunately, he doesn’t seem to understand that medicine is not the semiconductor industry. There’s a reason why we haven’t cured cancer yet, for example. It’s damned hard, and biomedical research does not lend itself easily to the sort of deadline-driven mentality that Groves had as CEO of Intel.

Derek Lowe put it well:

Mr. Grove, here’s the short form: medical research is different than semiconductor research. It’s harder. Ever seen one of those huge blow-ups of a chip’s architecture? It’s awe-inspiring, the amount of detail that’s crammed into such a small space. And guess what — it’s nothing, it’s the instructions on the back of a shampoo bottle compared to the complexity of a living system.

That’s partly because we didn’t build them. Making the things from the ground up is a real advantage when it comes to understanding them, but we started studying life after it had a few billion years head start. What’s more, Intel chips are (presumably) actively designed to be comprehensible and efficient, whereas living systems — sorry, Intelligent Design people — have been glued together by relentless random tinkering. Mr. Grove, you can print out the technical specs for your chips. We don’t have them for cells.

And believe me, there are a lot more different types of cells than there are chips. Think of the untold number of different bacteria, all mutating and evolving while you look at them. Move on to all the so-called simple organisms, your roundworms and fruit flies, which have occupied generations of scientists and still not given up their biggest and most important mysteries. Keep on until you hit the lower mammals, the rats and mice that we run our efficacy and tox models in. Notice how many different kinds there are, and reflect on how much we really know about how they differ from each other and from us. Now you’re ready for human patients, in all their huge, insane variety. Genetically we’re a mighty hodgepodge, and when you add environment to that it’s a wonder that any drug works at all.

It is, indeed.

None of this is to imply that we can’t improve our clinical trials system. As has been pointed out, it’s hugely expensive and inefficient, and these problems are getting worse with the evolution of drug treatment towards “personalized medicine.” We are going to have to figure out ways to make clinical trials smaller and more targeted. We are also going to have to find ways to extract every last bit of information and benefit out of every last clinical trials subject. An approach such as what Groves proposes might well contribute to achieving that aim, particularly when coupled with new trial designs that emphasize the incorporation of biomarkers for drug response. Contrary to Andy Groves’ claims, however, there is no way his sort of approach will ever replace well-designed clinical trials.

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Note: This was originally published as a “SkepDoc” column in Skeptic magazine under the title “Aspartame: Safe Sweetener or Perilous Poison?” and is reprinted here with the kind permission of Michael Shermer. There are other artificial sweeteners not specifically addressed here, but as far as I know there are no convincing health concerns about any of them, just this same kind of hype and fearmongering based on animal studies and speculation with no validation from human clinical studies.

Aspartame is a low calorie sugar substitute marketed under brand names like Equal and Nutrasweet. It is a combination of two amino acids: L-aspartic acid and L-phenylalanine. It is available as individual packets for adding to foods and it is a component of many diet soft drinks and other reduced-calorie foods. Depending on who you listen to, it is either a safe aid to weight loss and diabetes control or it is evil incarnate, a deadly poison that is devastating the health of consumers.

A reader sent me an ad from his local newspaper that recommended using stevia instead of aspartame and made these startling claims about aspartame:

1. It is derived from the excrement of genetically modified E. coli bacteria
2. Upon ingestion, it breaks down into aspartic acid, phenylalanine, methanol, formaldehyde, and formic acid.
3. It accounts for over 75% of the adverse reactions to food additives reported to the FDA each year including seizures, migraines, dizzinesss, nausea, muscle spasms, weight gain, depression, fatigue, irritability, heart palpitations, breathing difficulties, anxiety, tinnitus, schizophrenia and death.

Let’s look at those claims one by one.

1. In some markets, aspartame manufacture takes advantage of modern genetic laboratory processes. A plasmid introduces genes into E. coli bacteria; the genes are incorporated into the bacterial DNA and they increase production of enzymes that enhance the production of phenylalanine. The bacteria produce more phenylalanine, serving as little living factories. The phenylalanine these workhorses produce for us is exactly the same as phenylalanine from any other source.  It is disingenuous and inflammatory to characterize it as “derived from excrement.”  Genetic processes like this are widely used today. One stunning example is Humulin. Diabetics used to develop allergic reactions to the beef and pork antigens in insulin derived from cows and pigs because it was slightly different from human insulin and contained impurities. Scientists found a way to put human insulin genes into E. coli bacteria and put them to work producing true, pure human insulin. This was such a great advantage to diabetics that animal insulins are no longer even available.
2. Some of the things we ingest are directly absorbed and utilized unchanged, like water. But most of what we ingest is metabolized.  Aspartame is metabolized. It does indeed break down into aspartic acid, phenylalanine, and methanol.  Aspartic acid and phenylalanine are amino acids that we need to survive. Methanol is produced in small amounts by the metabolism of many foods; it is harmless in small amounts. A cup of tomato juice produces six times as much methanol as a cup of diet soda. Methanol is completely metabolized via formaldehyde to formic acid; no formaldehyde remains. Lastly, the formic acid is broken down into water and carbon dioxide. Human studies show that formic acid is eliminated faster than it is formed after ingestion of aspartic acid.  So yes, those compounds appear, but so what?  We get much larger amounts of the same compounds from our food, and they don’t hurt us.
3. I searched for documentation of that claim, and I couldn’t find the 75% figure anywhere. What I did find was that FD&C dyes (not aspartame) are the food additives most frequently associated with adverse reactions. Anyway, a list of reported adverse reactions is meaningless by itself. People can report any symptom they noticed after using aspartame, but they can be fooled by the post hoc ergo propter hoc fallacy: just because a symptom occurred after ingesting aspartame, that doesn’t prove aspartame caused the symptom. Controlled studies are needed to determine if the symptom occurred more often in people using aspartame than in people not using it. Many such studies have been done and have not shown a correlation of aspartame use with any of those symptoms.

Internet Hoax

So the ad amounts to scare tactics based on false and distorted information. Actually, this ad is pretty mild compared to some of the alarmist misinformation circulating on the Internet. There we are told that there is a widespread epidemic of aspartame poisoning, causing headaches, seizures, Alzheimer’s, cancer, diabetes, blindness, multiple sclerosis, birth defects, even Gulf War Syndrome. We are told that  “If you…suffer from fibromyalgia symptoms, spasms, shooting pains, numbness in your legs, cramps, vertigo, dizziness, headaches, tinnitus, joint pain, depression, anxiety attacks, slurred speech, blurred vision, or memory loss-you probably have ASPARTAME DISEASE!” We are expected to believe the lie that “When they remove brain tumors, they have found high levels of aspartame in them.”

All this misinformation has been identified as a hoax, an urban legend, by various sources including Time.com, Snopes.com and About.com. Much of it hinges on a widely disseminated e-mail by a “Nancy Markle” who was accused of plagiarizing it from Betty Martini. Martini is the founder of Mission Possible World Health International, which is “committed to removing the deadly chemical aspartame from our food.” She is also anti-vaccine, anti-fluoride, anti-MSG, a conspiracy theorist, and thinks she was cured of breast cancer by an herbal formula.

Her website consists of misinformation, testimonials, and hysterical rants. She implores readers:  YOUR personal horror story needed NOW!. She is associated with a number of others notorious for circulating unreliable information, including the infamous Joseph Mercola.

There’s even a book, Sweet Poison, by Janet Hull, creator of the Aspartame Detox Program.

Scientific Studies

Aspartame has been found to be safe for human consumption by the regulatory agencies of more than ninety countries worldwide, with FDA officials describing aspartame as “one of the most thoroughly tested and studied food additives the agency has ever approved” and its safety as “clear cut.”

When the European Commission’s Scientific Committee on Food evaluated aspartame, they found over 500 papers on aspartame published between 1988 and 2001. It has been studied in animals, in various human populations including infants, children, women, obese adults, diabetics, and lactating women. Numerous studies have ruled out any association with headaches, seizures, behavior, cognition, mood, allergic reactions, and other conditions. It has been evaluated far more extensively than any other food additive.

When new rat studies by the Ramazzini Foundation in Italy appeared to show an association with tumors, the European Food Safety Authority examined Ramazzini’s raw data and found errors that made them discredit the studies. Their updated opinion based on all the data available in 2009 said there was no indication of any genotoxic or carcinogenic potential of aspartame and that there was no reason to revise their previously established ADI (Acceptable Daily Intake) for aspartame of 40 mg/kg/day.  Studies have shown that actual consumption is well below that limit.

People who are absolutely convinced they get adverse effects from aspartame have been proven wrong. For instance, the New England Journal of Medicine published a study of people who reported having headaches repeatedly after consuming aspartame. When they knew what they were consuming, 100% of them had headaches. In a double blind crossover trial, when they didn’t know what they were getting, 35% had headaches after aspartame, and 45% had headaches after placebo.

Is Stevia Safer?

Stevia comes from a plant, and the Guaraní Indians of South America have been using it to sweeten their yerba mate for centuries. The “natural fallacy” and the “ancient wisdom fallacy” sway many consumers, but for those of us who are critical thinkers, who want to avoid logical fallacies and look at the scientific evidence, what does science tell us? Is stevia preferable to aspartame?  We really don’t know. Concerns have been raised about possible adverse effects such as cancer and birth defects. Stevia is banned in most European countries and in Singapore and Hong Kong because their regulatory agencies felt that there was insufficient toxicological evidence to demonstrate its safety. The US banned its import in 1991 as a food additive, but the 1994 Diet Supplement Health and Education Act (DSHEA) legalized its sale as a dietary supplement. Most of the safety concerns have been dismissed, but so have the concerns about aspartame. Arguably, the concerns about stevia are more valid than those about aspartame, because there is less evidence refuting them.

The plant extract is refined using ethanol, methanol, crystallization and separation technologies to separate the various glycoside molecules. The Coca-Cola Company sells it as Truvia. Pepsi sells it as PureVia. It is a product of major corporations and is prepared in a laboratory using “toxic” chemicals like methanol. For some reason that doesn’t bother those who are promoting stevia as a natural product.

What about HFCS?

High fructose corn syrup (HFCS) is also being demonized. “High” fructose isn’t really so high. HFCS is 55% fructose. Sucrose (table sugar) is 50% fructose and 50% glucose. Honey is 50% fructose. Apples have 57% fructose; pears have 64%.  Fructose has been blamed for obesity, diabetes, heart disease and a wide variety of other illnesses, but the evidence is inconclusive.  Avoiding fructose would mean avoiding all sources of fructose, not just HFCS. Avoiding fruit is probably not healthy. An International Life Sciences Institute (ILSI) Expert Panel concluded that “there is no basis for recommending increases or decreases in [fructose] use in the general food supply or in special dietary use products.” HFCS is 25% sweeter than sucrose, so you can use less of it and get fewer calories. Limiting total calorie intake is healthy, and both HFCS and aspartame can contribute to that goal.

Is Aspartame Safe?

Yes! For everyone except people who have the genetic disorder phenylketonuria (PKU). They must avoid aspartame because they can’t process phenylalanine and accumulated high levels of phenylalanine can damage their brains. Science has adequately demonstrated that aspartame is safe for everyone else.

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Parenting an infant can be totally overwhelming. One of the earliest challenge many face is learning to deal with periods of intractable crying. I often speak with sleep deprived parents when they’re looking for something — anything — to stop their baby from crying. They’ve typically been told by friends of family that their baby must have “colic” and they’ve come to the pharmacy, looking for a treatment. Colic is common, affecting up to 40% of babies in the few months of life.

While distressing, colic is a diagnosis of exclusion — that it, it is given only after other causes have been ruled out (hunger, pain, fatigue, etc.). The most common definition for colic is fussing or crying for more than 3 hours per day, more than 3 days per week, for more than 3 weeks. These criteria, first proposed by Morris Wessel in 1954, continue to be used today. However, scientific evidence to explain the cause is lacking. Ideas proposed include:

• changes in gastrointestinal bacteria/flora
• food allergies
• lactose intolerance
• excess gas in stomach
• cramping or indigestion
• intolerance to substances in the breast milk
• behavioural issues secondary to parenting factors

Despite its intensity, colic resolves on its own with no interventions. By three months of age, colic has resolved in 60% of infants. By four months, it’s 90%. It sounds harmless and short-lived, but colic’s ability to induce stress in parents cannot be overstated. Parents may be angry, frustrated, depressed, exhausted, or just feel guilty, ascribing their baby’s cries to some parenting fault.

Given our lack of understanding of the true cause of colic, there’s no shortage of cures that have been proposed. From drugs, to supplements, to manual therapies, everyone has their preferred intervention. As a pharmacist, I’m usually asked about drug and non-drug treatments. In particular, I’m often asked about gripe water — a cocktail of different ingredients, involving some combination of herbs, sodium bicarbonate, sugar, and alcohol. Invented by pharmacist William Woodward in the 1800′s, gripe water was originally develop to treat the fevers of malaria. Over time, it was felt to be helpful for babies with colic — though no rigorous evaluation has ever been conducted [PDF].

So what does work for colic? My usual advice to parents starts with reassurance. It’s not bad parenting, and it will pass, given enough time. But the lack of a clear cause and simple solution is not satisfying to many that I speak with. A discussion of stress management, dietary changes, or feeding changes (all usually recommended as first-line approaches) leaves few satisfied. Some are determined to leave the pharmacy with something. “What about this?” they’ll say, gesturing to a product on the shelf. “Will this help?” And that’s when it’s time to distill the evidence. Nicely, we have two new complementary (I don’t mean that in the CAM sense) systematic reviews published in 2011 that, together, cover most of the common treatments. The first review, Infantile colic: A systematic review of medical and conventional therapies by Belinda Hall and associates in Victoria, Australia, looked at “conventional” treatments — drugs, behavioural therapy, and dietary changes. The second, Nutritional Supplements and Other complementary medicines for infantile colic: A systematic review, is from Rachel Perry, Katherine Hunt, and Edzard Ernst. It looked at CAM therapies — supplements, nutritional products, and manual therapies. The two reviews overlapped with respect to nutritional products. Both papers are behind paywalls — I’ll summarize the highlights of both reviews.

The Hall paper was published the Journal of Pediatrics and Child Health earlier this year. A systematic review, it sought to examine all randomized interventions, cohort studies, and quasi-experimental studies for colic. Despite the ubiquity of colic, there have been few proper evaluations done. In a 30-year search of the literature, only 19 published trials were identified: five on drug treatments, ten on nutritional interventions, and four on behavioural interventions. All studies of drug products had significant quality limitations, including a lack of blinding and randomization information, unclear statisitical analyses, and in one case, no comparison of baseline demographics.

• Simethicone is an “anti-foaming” agent believe to help consolidate air bubbles, leading to their expulsion. It’s found in dozens of products. Two trials compared crying duration — neither showed any significant effect. Overall, there’s fairly good evidence to suggest it is ineffective.
• Dicyclomine is an old drug, now used most frequently (with limited success) to treat irritable bowel syndrome. Again, like simethicone, there are two trials, neither of which suggest there’s any meaningful effects. In addition, it has a nasty side effect profile. On balance, the risk-benefit profile suggests it should be avoided.
• Cimetropium is backed by a single study noting a significant decrease in individual colic episodes, but reported side effects of increased drowsiness. That’s not surprising, given it’s a derivative of belladona. Cimetropium does not appear to be available in North America, the UK, or Australia, however. And in the absence of studies reproducing the effects, and a better evaluation of the toxicity, I’d be hesitant to recommend it anyway.

Nutritional interventions suffer from the same methodological limitations as the drug studies. A lack of proper blinding was the most common bias. Other deficiencies included a lack of baseline characteristics, and unclear definitions of colic. Keeping this in mind, the data look somewhat more promising than drugs. There are mixed results with low-allergenic formulas, with some trials showing modest effects, and others showing no improvements. Promising results were found in breastfed infants who were switched to casein hydrosylate formulas, reducing colic from over 7 hrs/day to just under 3 hrs/day. This finding seems consistent with other studies, but comparisons are complicated by different designs and products used. Low-allergen maternal diets have also been associated with improvements in several studies, though they all are subject to bias due to a lack of blinding. Bottom line: promising but unproven. At least these interventions have minimal risk.

What doesn’t work? High-fibre diets had no effect when evaluated. Nor does lactase (Lactaid). Behavioural interventions have not been shown to suggest any meaningful effects. Examples include modified parent-child interaction, contingent music, and that old standby, “car ride simulation”.

“Alternative” Treatments

From a science-based perspective, “alternative” medicine is a misnomer: when clinical evidence emerge to demonstrate unproven therapies are effective, they become accepted as part of medicine. In short, effective treatment is “medicine,” while ineffective or unproven treatments are not medicine. Yet many are used in the absence of evidence, under monikers like “alternative”, “complementary”, and more recently, “integrative”. In the second review, the authors also conducted a systematic review, identifying randomized controlled trials of children diagnosed with colic, and treated with any form complementary or alternative medicine. Trials needed some form of control (placebo, no treatment, etc.) and needed to measure an outcome like severity, quality-of-life, physiologic parameters, or a reduction in the need of medication or other consequence of treatment. Fifteen trials met inclusion criteria — and were too different to permit meta-analysis. About half were deemed to be of good methodologic quality. Few collected or reported safety data: reinforcing the erroneous assumption that that natural products are inherently safe.

Spinal manipulation — Four studies were found, with three showing results that were statistically significant, yet all three positive trials were noted to have multiple methodologic issues (lack of blinding, etc). The highest quality trial was the only double-blind, placebo-controlled study conducted. It showed no effect in outcomes according to parent reports or crying diaries. (As most of you are aware, Simon Singh has made the lack of evidence of chiropractic for colic quite well known.)

A double-blind comparison of Colimil (fennel, lemon balm, and German chamomile) was evaluated to be more effective than placebo. Again, methodologic problems and a lack of duplicative studies makes an evaluation difficult. Another small trial of fennel tea suggested a beneficial effect, too.

I’ve blogged previously how sugar solutions can provide analgesic effects to reduce vaccination distress. They’ve also been evaluated for colic. Like other interventions, some promising results are watered down by methodologic issues.

Is it a lack of beneficial bacteria in the gastrointestinal tract? Probiotic studies have reported positive effects, albiet with quality issues that included a lack of blinding. This paper also looked at nutritional studies, and flagged the same issues that the other review identified.

In a study of massage, both massage and a vibrating bed were reported to have beneficial effects. The improvement over the duration of the trial may have been due simply to the natural course of the condition. A single reflexology trial had problems with entry criteria and so many flaws it was not possible to drawn conclusions beyond the possible beneficial effects of touch alone.

Conclusion

It’s easy to give the TL;DR version of both reviews: Nothing has been convincingly demonstrated to be effective. And that shouldn’t be surprising. Given we don’t know the actual cause of colic (if there even is a single cause), our interventions are simply shots in the dark, meaning there’s little prior probability — and the data that emerge from these isolated trials becomes much less persuasive. With weak study designs, the probability of publication bias, and the lack of confirmatory data for most treatments, we’re left with some promising areas that require further study – and that’s about it.

But we can draw some conclusions of exclusion: There’s little evidence that conventional drug treatments are safe or effective. There’s also no evidence to suggest behavioural interventions, or manual therapies like chiropractic and massage have any effect. Dietary interventions appear to be the most promising type of treatment, followed by sugar solutions, and remotely, herbal products like fennel tea. While there are significant data quality issues with all trials, at least dietary interventions and sugar solutions have little risk. So for parents determined to try something, these interventions seem to offer the best risk/benefit perspective.  But the best, most effective intervention for colic remains the passage of time. Colic will pass. Reassurance is probably the best advice of all.

References

Hall B, Chesters J, & Robinson A (2011). Infantile colic: A systematic review of medical and conventional therapies. Journal of paediatrics and child health PMID: 21470331
Perry R, Hunt K, & Ernst E (2011). Nutritional supplements and other complementary medicines for infantile colic: a systematic review. Pediatrics, 127 (4), 720-33 PMID: 21444591

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Determining the net health effects of independent factors can be tricky, especially when those factors cannot be controlled for in experimental studies. For things like body mass index (BMI) we must rely on observational data and triangulate with multiple studies to isolate the contributions from BMI. But it can be done.

The data, however, are likely to be complex and noisy, and therefore there is plenty of opportunity for ideology to trump objectivity in interpreting the data. There are those who, for whatever reason, deny that we are having an obesity epidemic in the West, and those who deny the health implications of being overweight as an independent factor.

BMI

The terms overweight and obesity have had various definitions in the past, but in recent years the various health organizations have settled on consensus operational definitions (for obvious practical reasons). Their definition relates to body mass index, which is a person’s weight in kilograms (kg) divided by their height in meters (m) squared.

It should be noted that BMI is a measure of weight, not fat (adiposity). BMI is used for convenience, as height and weight data are often available, but more direct measures of body fat are not. It is widely recognized and admitted that BMI is problematic as applied to individuals. Muscular and athletic people may have a high BMI and not have excess adiposity, for example. Also at the extremes of height the BMI becomes harder to interpret.

But this does not mean the BMI is useless. In fact, for most people BMI correlates quite well with adiposity. In one study researchers compared BMI to a more direct measure of body fat percentage using skin-fold thickness. They found that when subjects met the criterion for obesity based upon BMI, they were truly obese by skin-fold thickness 50-80% of the time (depending on gender and ethnicity). When they were not obese by BMI they were not obese by skin-fold 85-99% of the time.

So BMI is a rough but useful estimate, good for large epidemiological studies where more elaborate fat percentage measurements are not practical. However, those who wish to deny the “obesity epidemic” have found BMI to be a convenient target for sowing doubt.

There is ongoing research into the utility of supplementing BMI with other easy measures, like waist circumference. This seems to be a more accurate measure of adiposity, and specifically risk from being overweight. So going forward we may see more meaningful measured routinely captured, and BMI may be replaced or supplemented with these measures. But for now we will continue to see many studies based upon BMI.

Overweight and Obese

Because BMI is a convenient measure, it has become the measure of choice in defining overweight and obesity. For children and adolescents overweight is defined as a BMI in the 85-95% percentile by age and gender, while obesity is >95% percentile BMI. For adults overweight is defined as a BMI of >=25.0 but <30.0, obese is defined by BMI >=30.0 and < 40.0, and extremely obese is defined as BMI >=40.0.

These cutoffs, like all such cutoffs for medical definitions, are partly arbitrary (they constitute drawing a line to demarcate a spectrum) but are evidence- based. This is similar to definitions for hypertension, for example. Researchers typically will set the cutoff to capture most people who are at risk for medical complications.

This is where the controversy comes into play with overweight and obesity. In 1998 the NIH decided to lower the cutoff for BMI for overweight, from 28 for men and 27 for women to 25 for both sexes. This was based upon an expert panel review of hundreds of studies. It also brought the NIH definition in line with the World Health Organization and other health organizations. The BMI 25 cutoff has now become generally accepted. The cutoff for obesity was not changed – it was and remains a BMI of 30.

Of course this means that any estimates of overweight (but not obesity) based upon the newer lower cutoff of BMI 25 would be greater than estimates based upon the previous criteria. This raised a bit of a kurfuffle, as it always seems to do when medical definitions are altered. This happened with the lowering of the cholesterol cutoff, blood pressure for hypertension, and blood sugar for diabetes.

This event in 1998 now has become a central argument in the arsenal of obesity deniers. If you search on “obesity statistics”, on the first page you will get this apparent libertarian site which quotes a “food industry spokesman” as saying:

In 1998, the U.S. Government changed the standards by which body mass index is measured. As a result, close to 30 million Americans were shifted from a government-approved weight to the overweight and obese category, without gaining an ounce, Burrita said.

This is slightly misleading, as the obese category was not changed. But the main point is that this 1998 redefinition is being used to argue that the obesity epidemic is all smoke and mirrors. The article goes on to quote this gem from William Quick:

According to an American Medical Association report, 14.5 % of Americans in 1980 were obese, a total of 32,700,000 (based on a population of 226,000,000). If, as the above article states, the numbers of obese Americans have “doubled” in the past twenty years, this would mean there are now about 66 million of them. But thirty million of those fatties were created by a change in definition, so by the standards of 1980 [we would calculate an] obesity percentage of 12.85 percent, an actual decrease in obesity percentage since 1980.

That’s some massively flawed reasoning. Again we see the confusion of the overweight and obese categories. But also there are many false assumptions in that back-of-the-envelope calculation. Quick is mixing statistics from different sources and contexts, and the result is a mess.

What we really need is a look at the numbers over time using the same definition. Fortunately, most epidemiologists are not dolts and they get this very basic concept. In fact, it doesn’t get much more basic than this, and it would take some pretty naive incompetence to use inconsistent definitions over time.

The CDC has crunched the numbers for us, and using the modern cutoffs for overweight, obese, and extremely obese applied to BMI data for the last few decades they document a pretty steady increase in American fatness over time. Take a look at the video on the site to see this data presented graphically. Also, it is summarized in the graph here.

As you can see, the lines go steadily up – with the exception that the overweight category has decreased in the last decade. However, it seems that this is due to the shifting of people from the overweight category to the obese category, not to the normal weight category.

Of course, you could cherry pick by just looking at the overweight category. Looking at all the data, however, tells the real story.

The Health Risks of Overweight

Is being overweight and obese an independent risk factor for any specific illness? The answer is an overwhelming yes. There are many diseases for which being overweight is a risk factor, such as type II diabetes, obstructive sleep apnea, pseudotumor cerebri, heart disease, and other illnesses. The data is clear – but complex, and so allows for those motivated to deny the connection to distort and cherry pick the data to create the impression they wish.

From a website advocating size acceptance we read:

There is actually no evidence that being fat will give you diabetes or cancer or PCOS or any other health issues. Being obese tends to correlate with some health problems, but the causes of the health problems may be multiple, and they certainly aren’t thoroughly understood in current medical research.

It must be pointed out that many obese people are perfectly healthy, if you look at the numbers that matter. This seems to refute the idea that fat alone causes artery clogging, diabetes, or anything else it’s often blamed for – clearly, there are at least other factors besides fat, and it may even be the case that fat’s nothing to do with it at all. As long as your other numbers are good, your weight does not impact your health. If you can possibly afford to get your numbers tested once a year, or even every few years, do so. If the numbers that matter are good, your weight is fine

Here we see a couple of logical fallacies. The first is the denial of cause based upon an overapplication of the “correlation does not equal causation” fallacy. It is true that correlation alone does not prove causation, but causation may be the answer, and we can test this hypothesis by testing multiple correlations. For example, if weight is reduced will the risk of the disease decrease.

Also, the fact that being overweight and obese may cause health problems through intermediary effects is irrelevant. If being overweight causes insulin resistance which causes diabetes, it is not meaningful to say that weight is not causing diabetes.

We also see confusion between weight as a risk factor vs being an absolute cause. Weight is one factor among many, such as genetics. There are obese people who are otherwise healthy, just like there are heavy smokers who never get lung cancer. This is entirely irrelevant to the claim that weight is a risk factor for various diseases. The lack of 100% correlation does not justify the conclusion that weight has “nothing to do with it at all.”

Conclusion

There is an obesity epidemic in the US and in developed nations generally, and this increase in adiposity is an independent risk factor for many diseases and disorders. Exactly what role weight is playing in specific diseases is a complex question that is the subject of ongoing research, but there is already overwhelming data in many condition to show that being overweight is a health risk.

Further – this has nothing to do with size acceptance. We can separate the question of social stigma from the medical facts. It is also folly to tie a social/ethical issue to a specific factual premise – because when the facts don’t come out the way you wish that either weakens your ethical stance, and/or forces you to deny the scientific facts. We can simultaneously treat overweight and obesity as the health problem that it is, while addressing the social and psychological aspects of weight in our society.

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A board certification in woo?

I’ve been harshly critical of the entire concept of “integrative medicine” (IM), which has over the last few years nearly supplanted the former term used for non-science-based medicine or medicine based on prescientific ideas represented as though it were scientific medicine, “complementary and alternative medicine” (CAM). Indeed, just last week I pointed out how IM is far more about marketing than it is about science or medicine, and over the last three years I’ve been particularly harsh on the concept of “integrative oncology,” which is actually being represented as a “subspecialty” of IM. Despite the utter lack of a rationale based on science or the scientific basis of medicine, IM has still been making inroads into academic medical centers, where I tend to refer to it with the unapologetically disparaging term “quackademic medicine.” Even worse, now, increasingly, such woo has been insinuating its way into community medical centers as well.

Arguably, the man who has done more than any individual to promote the quackification of science-based medicine is Dr. Andrew Weil. (At least, I can’t think of any single person who’s done more during his lifetime to promote the infiltration of quackery into medicine. Readers are free to chime in if they know of someone who could challenge Weil for the title of King of Quackademic Medicine.) As I pointed out the last time I discussed him, Dr. Weil doesn’t really like science-based medicine. Oh, no, he doesn’t like it at all. Unfortunately, he’s been very successful in promoting quackademic medicine. He’s also arguably been the single most successful person at legitimizing what used to be viewed as quackery. Master of the domain of “integrative medicine,” having formed a model of an “integrative medicine in residency” that’s spread like kudzu through quackademia, all from his redoubt at the University of Arizona, Dr. Weil has now announced his intention for the next phase of his “integrating” pseudoscience with SBM. I learn this from The Integrator Blog, which has as a recent headline from last week Special Report: “Strategic Change in Direction” as Weil’s Arizona Center Commits to Creation of American Board of Integrative Medicine:

In a major strategic shift, the University of Arizona Center for Integrative Medicine (ACIM) has announced that it will lead the creation of a formal specialty for medical doctors in integrative medicine. ACIM, founded by Andrew Weil, MD and directed by Victoria Maizes, MD, is in dialogue with the American Board of Physician Specialties toward establishing an American Board of Integrative Medicine. They are collaborating with leaders of the American Board of Integrative and Holistic Medicine (ABIHM). Here is the ACIM announcement, a statement from two ABIHM leaders, a brief interview with Maizes and the list of 18 founding Board members. Is this the right strategic choice? What impact will this have on integrative medicine and the broader integrative healthcare movement?

At first, I wasn’t aware that this was, in fact, any sort of “strategic shift.” Being recognized as a medical specialty, complete with standards for an educational curriculum during residency or fellowship and board exams for certification, is the ultimate validation of legitimacy as a medical specialty, at least as far as medical education, regulation, and the overall medical world goes. If Dr. Weil could achieve this, it would become virtually impossible to eliminate woo from medicine, at least in the United States. It would be codified as a medical specialty by one of the three major certifying boards that certify physicians as being qualified in specific specialties, in this case the American Board of Physician Specialties (ABPS). The other boards include American Osteopathic Association Bureau of Osteopathic Specialists (which only certifies doctors with the DO degree) and the American Board of Medical Specialties. Of these, the last one, the ABMS, is the board that really matters in most states. For instance, the board under which I’m Board-certified in Surgery is, appropriately enough, the American Board of Surgery. The ABS is the umbrella board that certifies surgeons in General Surgery, Vascular Surgery, Pediatric Surgery, Surgical Critical Care, Hand Surgery, and others. In addition, the ABMS certifies 23 other specialties, including Anesthesiology, Emergency Medicine, Internal Medicine, Pathology, Pediatrics, and many others. These boards set up minimum standards for knowledge and skills and devise tests and documentation necessary to be “certified.” Generally, board certification requires an MD or DO degree, completion of an accredited residency in the relevant specialty, and the passing of written and oral examinations. Some specialties require documentation of practice results (such as plastic surgery, which requires a case log, complete with “before and after” photos)

One thing that our non-U.S. readers might find odd (and that a surprising number of U.S. residents don’t even know) is that there is no national licensure of physicians in the United States. Each state writes its own laws and has its own medical board. It is also necessary to understand that board certification is an entirely separate process from state licensure. In fact, you don’t have to be board-certified to have a medical license; in most states, all you have to have is a medical degree and a year of postgraduate training (internship). Indeed, I got my first medical license during my residency, long before I ever achieved Board certification in Surgery. In fact, in the old days, it was entirely possible to practice for an entire career without being board certified, and many physicians did just that. There are even a few older physicians left who still practice without board certification, having in effect been “grandfathered” into the system. These days, however, if you want to be on the staff of a hospital or be an approved provider on an insurance plan, you pretty much have to be board certified in your specialty. If you’re not, you’ll be permanently consigned to a lower tier of practice, such as moonlighting jobs or jobs as “house physicians” who cover patients in hospitals without residents during nights and weekends. Exceptions are sometimes made in rural hospitals that are desperate for physicians, but even these exceptions are disappearing. Basically, in order to practice as a fully independent professional in the United States, you have to be board-certified or board eligible.

So why would Dr. Weil want to change course and seek a form of board certification for IM? Here’s how Dr. Weil himself describes the reason in the University of Arizona press release:

We are writing to let you know about an important decision that we recently made — a decision that represents a strategic change in direction for our Center. For many years we have resisted the idea of board certification in Integrative Medicine (IM). We have always believed that the principles and practices of IM should inform all specialties, rather than be developed into a new field. In other words, that dermatologists, surgeons, and family physicians alike all need to learn the principles of nutrition and mind-body medicine, and to value the innate healing capacity of the body. We still hold that belief.

But…

Earlier this year we approached the American Board of Physician Specialties (ABPS) to discuss creating a board in IM. We did so for many reasons; chief among them was to help patients discern who truly has training and expertise in IM. It is now popular in the marketplace to say you practice IM — yet anyone can say so, whether they studied for an hour, a weekend, or ten years.

This is actually pretty hilarious in its own way. This is almost the same reason that virtually every subspecialty that has ever applied to have a board certification process has cited as its reason for doing so. The reasons such a consideration almost inevitably come down to protecting the reputation of the specialty by defining who is and is not a member of the specialty. Apparently the desire to infuse all medical specialties with his woo cannot stand up to the cold, hard reality of how medicine really works. So now he wants his own boarded specialty, because he realizes that the only way IM will ever be taken seriously by patients is for it to be its own boarded specialty. Never mind where the board certification comes from, which currently is a highly dubious “board.”

The actual board that would be overseeing any board certification in IM would be, according to the press release the American Board of Integrative Holistic Medicine (ABIHM). This board was first formed in 1996 as the American Board of Holistic Medicine. A quick perusal of its FAQ regarding certification reveals a number of interesting things. First, the only qualifications necessary to sit for the ABIHM boards are (1) and MD or DO; (2) a current medical license in the U.S. or Canada; and (3) board certification or board eligibility in a specialty accredited by the Accreditation Council for Graduate Medical Education (ACGME). That’s it. No training program. No residency program in “holistic medicine,” “integrative medicine,” “complementary and alternative medicine,” or anything at all. You could be a radiologist, pathologist, or other specialties that don’t generally directly care for patients. In other words, if you’re a physician who’s board-certified or board-eligible in any currently recognized medical specialty, all you have to do to be board certified in IM is to take the test and pass it, which 85-90% of those who take it do on the first try and those who don’t can try again. Indeed, the ABIHM sends applicants its Course Curriculum Study Guide (CCSG) and recommends that applicants “be very familiar with the material in the CCSG before you sit for the exam.” The ABIHM also provides a review course but doesn’t require it.

You know, it’s half tempting for me to register for the exam and see if I can become a board-certified practitioner of IM. There’s nothing that says I can’t do it, and I’d get access to the review materials, which, I suspect, would be most illuminating. For example, how much homeopathy would I be expected to know? Acupuncture? Would I have to memorize meridians and acupuncture points? Would I have to know how to do reiki? Inquiring minds want to know, although this inquiring mind doesn’t want to know badly enough to pay the $800 it would take to register. Perhaps there are other, richer physicians who might want to go that route. If so, the deadline to get the cheap rate to take the test on November 12 is October 3.

John Weeks of The Integrator Blog describes a “town versus gown” divide in IM, in which the “townies” (i.e., the private practice, non-academic IM practitioners) very much wanted some sort of board certification, while the “gowns” (i.e., the centers of quackademic medicine) did not. He doesn’t really elaborate on the reasons for this conflict but points out that the name change to ABIHM was driven by a desire to “raise standards.” Of course, when one is discussing healing modalities not based in science but rather in prescientific mystical thinking, such as acupuncture, reiki, homeopathy, and the like, one can’t help but think that “raising standards” would involve eliminating such modalities from medicine altogether. Be that as it may, I find it rather telling as to why Dr. Weil chose to go the route he did, choosing a third rate certifying board over the certifying board that is generally recognized by every state, hospital, and insurance company:

Unlike the American Board of Medical Specialties (ABMS), which would require approval by every single specialty board, ABPS is interested in creating a single pathway, recognizes fellowship training, and is an innovator. We had hoped the ABMS would consider a Certificate of Added Qualification in IM — such as exists for geriatrics — which can be applied for by different residency specialties; but ABMS is eliminating that concept.

Our goal is to have all graduates of our 1000-hour fellowship become board certified. At the same time we have not relinquished our goal of bringing IM training to all physicians. The success of our Integrative Medicine in Residency makes us comfortable and confident that IM will become a part of all physicians’ basic training. This 200-hour program is being used in 22 family medicine and two internal medicine residencies. In 2012 we will begin a pilot in two pediatrics residencies.

This is an exciting step for the field of Integrative Medicine (IM). Board certification is widely recognized by physicians and the public alike as a critical step in establishing a field. The first meeting of the American Board of Integrative Medicine will take place in Tampa, Florida, October 10-11. Over a two-year period, we will set criteria for sitting for the board exam and develop a validated exam.

In other words, the ABMS had standards that were too high for Dr. Weil, whereas the ABPS is not. Let’s just put it this way. “Innovation” is not really what I want in a certifying board for a medical specialty. I prefer a boring dedication to science-based practice and a caution that leads new specialty acceptance to be evolutionary rather than revolutionary.

An end run around standards

Believe it or not, before I saw Dr. Weil’s press release and started doing a bit of research for this post, I had never heard of the AAPS or its companion board the ABPS. After all, the ABMS is the gold standard board through which the vast majority of physicians in this country are certified. Indeed, my very own specialty, surgical oncology, is not a boarded specialty at present. There are training programs approved by the Society of Surgical Oncology, but these fellowships do not lead to sitting for boards, and surgical oncology is viewed mainly as an offshoot of general surgery. Indeed, ever since I decided that I wanted to go into surgical oncology in the mid-1990s (and long before my entry into the field), there has been a debate over what surgical oncology is as a specialty and whether it should be fully distinct from general surgery. Remember that most cancer operations for breast cancer, GI malignancies, melanoma, and some other cancers have long been the purview of general surgeonss and even today in the U.S. most such operations are still carried out by general surgeons in the community. Surgical oncology, as envisioned, was originally going to cover more complex cancer operations, those needed by patients referred to tertiary medical centers and cancer centers like Memorial Sloan-Kettering and M.D. Anderson Cancer Centers. There was also, let’s face it, the question of turf. For example, multiple surgical specialties claim colon cancer as part of their areas of special expertise, including (now) general surgery, colorectal surgery, surgical oncology, and, increasingly, minimally invasive surgery.

The lack of board certification for surgical oncology is a situation that will not last much longer, though. It was announced at the SSO Meeting in March 2011 that, after decades of trying, the SSO had finally managed to win board certification for surgical oncology from the ABMS. The new board certification will be called Complex General Surgical Oncology and will be a subspecialty board under the ABS. It will require board certification in general surgery, plus fellowship training of at least two years beyond that in an approved fellowship program, followed by passing a board examination in surgical oncology.

Another interesting aspect of board certification in Complex General Surgical Oncology is that current practitioners and graduates of even approved surgical oncology training programs will not be grandfathered in. Whenever a new subspecialty peels off from an established, more general specialty, such as when vascular surgery peeled off of general surgery to become a recognized specialty, inevitably there are cries from current practitioners of that specialty for a mechanism to “grandfather” them in and provide a means for them to become board certified too without having to undergo residency or fellowship training again. For example, I am rapidly finishing my fifth decade of life; going back to a fellowship is not practical, nor would it be for the vast majority of mid-career surgeons like me with a lot of experience but also 15-20 years (or even more) left in their careers. This would be the case even if there were enough fellowship slots to accommodate them and surgeons finishing residency, which there are not. In marked contrast, every report I’ve seen about the new certificate in Complex General Surgical Oncology at SSO meetings over the last few years indicates that current surgical oncologists will not be able to take the examination and be grandfathered in. That includes even the eminent surgical oncologists who are the founding members of this new board. Unless I go back and do a surgical oncology fellowship again, I can never be board certified in surgical oncology. (No doubt some quack will attack me for that ten years from now, after the new system has started to crank out a significant number of board certified surgical oncologists.)

Readers might be thinking to themselves right now, “That’s all very interesting, Gorski (well, not really), but why are you explaining this? What does any of this have to do with board certification in IM?” I answer: Compare and contrast, my friends. Compare and contrast. Dr. Weil could have tried to partner with the much more respected and authoritative ABMS. Why didn’t he? Because, at least for now, the ABMS wouldn’t touch this “integrative” woo with the proverbial ten foot pool (Weil et al. even admit that in their press release). Don’t get me wrong. Given the infiltration of quackademic medicine into so many medical schools and academic medical centers, I’m under no illusion at all that the ABMS is so science-based that this situation might not change in the future and it might not become more “open” to IM, but at least for now, the ABMS appears not to be interested in pseudoscience-based medical pseudo specialties. That is, of course, a good thing. In contrast, the AAPS is apparently—shall we say?—more “open minded.” Indeed, take a look at this video from the AAPS website describing board certification through the ABPS:

Notice the arguments? “Who’s got your back?” Fight against unfair “discrimination against deserving physicians.” The ABPS has a “big tent approach to medicine.” “You’re not a mere number” with ABPS. I don’t know about you, but I know that I want a “big tent” approach to medicine. A “big tent” approach is a major reason why quackademic medicine has gotten as far as it has. For example, apparently the AAPS has been having difficulty getting its emergency medicine boards recognized because it doesn’t require a specific emergency medicine residency and is mounting a major public relations and lobbying campaign to change that, with the goal of being recognized in every state (which of course means ABPS certifications in emergency medicine are not recognized in some states:

“We have a very aggressive and active governmental affairs program for 2010,” said Timothy Bell, the AAPS director of governmental affairs. “Our strategic plan for 2010 includes Alaska, Montana, Idaho, Utah, and North and South Dakota. It will put us on the path of achieving the goal of being recognized in every state.”

The plan puts ABPS on a collision course with the American Board of Medical Specialties as well as the Bureau of Osteopathic Specialists and Boards of Certification of the American Osteopathic Association, the most widely accepted agencies for medical specialty certification. Nowhere is the clash more evident than in the field of emergency medicine, perhaps because of the Daniel v. ABEM suit that spanned 15 years, casting a shadow over the field’s attempt to move from grandfathering for the field’s pioneers, who had no chance to enter an emergency medicine residency, to a residency-based approach. While ABEM bases board certification on completing an emergency medicine residency and testing, ABPS’s certifying body, the Board of Certification in Emergency Medicine (BCEM), allows applicants to have completed a primary care or anesthesiology residency along with 7,000 hours of experience in an emergency department.

Hmmm. Maybe I should see if the ABPS will set up a competing board in surgical oncology, so that I can be board-certified too! In any case, New York and Oklahoma, at least, have recently thwarted the ABPS initiative. Meanwhile, relatively few hospitals recognize ABPS certification as being “board certified,” and the American College of Emergency Physicians does not recognize the ABPS as a valid certifying body. Neither does the American College of Surgeons.

Seen in the light of the example of emergency medicine, it’s very clear why Dr. Weil and the ABIHM chose the ABPS. First, unlike leaders in surgical oncology, Dr. Weil didn’t want to go through what could be a decades-long (or more) process of convincing the ABMS that “integrative medicine” is a valid and distinct medical specialty. Second, the ABMS has made it clear that it’s not going to “grandfather” practitioners in, whereas the ABIHM almost advertises that you should take its test now while things are still easy, before the ABIHM institutes an IM residency requirement for its board certification:

Within the next few years, the ABIHM has plans to phase out the certification of physicians without formal training from an integrative medicine residency or fellowship program. We will also be raising the benchmark for passing the exam. Thus, physicians without formal training have a time limited opportunity to become Diplomates before the new standards are implemented. Our intent is to offer “grandparent” status to those who underwent certification prior to the installment of the upgraded requirements.

Get yer IM board certification while they last at this low, low price of $800 and no special residency needed!

The bottom line

There is little doubt that Dr. Weil has realized that his specialty of IM is, despite his massive success in infiltrating quackademic medicine into medical academia, still not taken seriously where it matters, namely by certifying boards, state medical boards, and, of course, insurance companies. If he can succeed in creating a medical specialty that appears legitimate based on board certification, then recognition by state medical boards and, more importantly, third party payers might well follow. If it takes partnering with an umbrella organization for various medical boards that aren’t as well-accepted and well-respected as those under the umbrella of the ABMS, so be it. Most of the public doesn’t know the difference, anyway. So Dr. Weil and a bunch of buddies, including people we’ve discussed before on SBM such as Dr. Mimi Guarneri (who was the pro-IM counterpoint to Steve Novella when he was on The Doctor Oz Show last spring), Dr. Brian Berman (who’s managed to slip bad acupuncture papers past reviewers into high impact journals), and Dr. Benjamin Kligler (who’s the research director in integrative family medicine for the Beth Israel-affiliated Continuum Center for Health and Healing), among others, got together and formed the American Board of Integrative Medicine.

One potential consequence of this effort might well be ticking off non-MD practitioners of woo such as naturopaths. John Weeks even mentions this as a possibility:

This strategic decision by ACIM has many dimensions. There are clear public health implications. The ACIM-ABIHM alliance represents a significant new alignment. Grassroots access to the “integrative medical doctor” title or at least board certification may disappear. There are guild dimensions here, ground claiming, and not just for IM doctors. Many naturopathic doctors and acupuncturists and chiropractors use the term. The brand “integrative medicine” may become even more closely associated with, and effectively owned by, medical doctors. New clarities will emerge, new boundaries will be drawn, new possibilities empowered.

Indeed. I rather suspect that this is a blatant effort of the “MD wing” of the alternative medicine world to claim the specialty for itself and push out all the “riff raff,” like naturopaths, homeopaths, chiropractors, acupuncturists, and the like by preventing them from using the term “integrative medicine” to describe what they do. One potential result, if Weil and his merry band of woo-meisters are successful, is to marginalize non-MD practitioners, which might not be a bad thing from the point of view of science-based medicine. What would be a bad thing is that it would simultaneously allow MDs like Weil to lay claim to the woo inherent in IM in order to give it the patina of legitimacy that, despite 20 years of the best efforts of doctors like Weil, IM or CAM or whatever the pseudorespectable nom du jour is still doesn’t have and doesn’t deserve because much of it consists either of Trojan horses or pseudoscience.

Whatever happens, one consequence that will not result from this effort is any improvement in patient care.

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There has been an ongoing debate about placebos on SBM, both in the articles and in the comments. What does it mean that a treatment has been shown to be “no better than placebo?”  If our goal is for patients to feel better and they feel better with placebos, why not prescribe them? Do placebos actually do anything useful? What can science tell us about why a patient might report diminished pain after taking an inert sugar pill? The subject is complex and prone to misconceptions. A recent podcast interview offers a breakthrough in understanding.

On her Brain Science Podcast Dr. Ginger Campbell interviewed Dr. Fabrizio Benedetti, a physician and clinical neurophysiologist who is one of the world’s leading researchers on the neurobiology of placebos. A transcript of the interview [PDF] is available on her website for those who prefer reading to listening. The information Dr. Benedetti presents and the expanded remarks by Dr. Campbell after the interview go a long way towards explaining the placebo phenomenon and its consequences for clinical medicine. Dr. Campbell also includes a handy list of references. I’ll try to provide a summary of the main points, but I recommend reading or listening to the original.

A common misconception is that the response to placebos is a purely subjective psychological response involving only the cortical level of the brain; but evidence is accumulating that real, measurable, objective subcortical neurophysiologic phenomena are involved. One of the first hints was a 1978 study showing that the placebo response to pain could be blocked by naloxone, a narcotic antagonist drug, indicating that the placebo must have actually caused an increase in endogenous opioids.

Placebos are used in clinical trials methodology, where a placebo group is compared to an active treatment group. Typically, about a third of subjects in the placebo group show improvement, but this doesn’t mean all of them have responded to the placebo. There are many other factors that can cause improvement after administration of any treatment, whether effective drug or placebo, including spontaneous remission, regression to the mean, and various kinds of bias on the part of patients and experimenters.

Clinical trials are done to look for a difference between the outcomes with placebo and the outcomes with the drug. Researchers in those trials are not interested in trying to understand why there is an improvement in the placebo group. That requires a different kind of study. Dr. Benedetti is using “placebo balanced design” to tease out the influence of verbal suggestions — expectations — on the action of drugs. Subjects are divided into four groups. The first group of subjects receives the active treatment and is told it is the active treatment (the truth).  The second group receives the active treatment and is told it is placebo (a lie). The third group receives placebo and is told it is the active treatment (a lie). The fourth group receives placebo and is told it is placebo (the truth). This design allows researchers to separate the specific effects of the active treatment itself from the nonspecific effects of suggestion and expectation.

In studies of surreptitious vs. open IV morphine administration, patients experienced less pain relief from the morphine when they were unaware that they were getting it. In one brain imaging study, the metabolic response to methylphenidate decreased by 50% when subjects were told they were getting a placebo.

The placebo response is not limited to pain. In Parkinson’s disease, placebos have been shown to cause a 200% increase in dopamine release in the brain, with an alteration in the activity of neurons and a corresponding clinical improvement in motor function. Dr. Benedetti has even documented a physiologic placebo response at the level of single neurons. In deep brain stimulation studies, the stimulator doesn’t work as well if patients are told it is off when it is actually on.

There is not just one “placebo effect,” but many different placebo effects that work by different mechanisms, including (1) anxiety reduction, (2) activation of the reward mechanism (with dopamine release in the nucleus accumbens), and (3) learning.

Placebo responses can be divided into two types: conscious and unconscious. Conscious responses involve suggestion and expectation. Unconscious responses occur with classical Pavlovian conditioning.  If you give morphine 3 days in a row and on the 4^th day you replace it with a placebo, almost 100% of patients will respond to the placebo as if they had received morphine. When a pill is administered, there is a completely unconscious association between two stimuli: the pharmacologic effect and the psychosocial context, which may include such things as the color and shape of the pill. Unconscious conditioning has been demonstrated in both animals and humans.

Conscious expectations are important for conscious physiological functions like pain and motor performance. Unconscious conditioning is more important for unconscious physiological functions like hormone secretion and activation of different immune mediators. Dr. Benedetti gives this example: if you give a patient a placebo and tell him it will increase his growth hormone levels, nothing happens. But if you give a drug that really does raise GH levels for two days and on the third day replace it with a placebo, the levels will rise with the placebo.

Clinical Implications

Dr. Benedetti gives placebos to subjects in a research setting; he doesn’t recommend giving them to patients in the doctor’s office. Placebo studies are important for understanding how the brain works, but Dr. Benedetti is not sure that they will lead to any clinical application. He says

the take-home message for clinicians, for physicians, for all health professionals is that their words, behaviors, attitudes are very important, and move a lot of molecules in the patient’s brain. So, what they say, what they do in routine clinical practice is very, very important, because the brain of the patient changes sometimes… there is a reduction in anxiety; but we know that there is a real change…in the patient’s brain which is due to… the ‘ritual of the therapeutic act.’

Experimentally, morphine requirements can be reduced by starting with morphine, substituting a placebo for later doses and periodically reinforcing the conditioning with morphine. This sounds like a good thing, but before it could become a useful option in clinical practice, it would have to overcome a number of ethical and practical hurdles. The unconscious placebo responses require conditioning and the conscious ones are problematic too. Even if some patients might get a degree of pain relief from just being handed a sugar pill with a strong suggestion, the effects can’t compete with effective pain treatments: the response is generally smaller, less reliable, less predictable, and not sustainable over the long term. I can’t imagine that ever becoming standard medical practice, and not just because of the ethical issues.

The doctor-patient relationship is essential to medicine, and placebo effects are an inherent part of that interaction. Communication is vital. Doctors must tell patients what a treatment is supposed to do. When pain medication is given without the patient’s knowledge, it doesn’t work as well. A clear understanding of the diagnosis is important: a positive diagnosis of something menacing like cancer can make the patient anxious and more aware of symptoms, while a negative diagnosis can reassure, relieve anxiety, and divert attention elsewhere. Lying to patients would undermine a trusting doctor-patient relationship and ultimately even interfere with the ability to evoke placebo responses. Prescribing placebos is uniformly rejected by medical ethicists: instead, we can put our increasing knowledge of placebo neurophysiology to good use without lying to patients.

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Like most people who grew up after April 22, 1970, I think it is important to be as environmentally responsible as possible.  Like many I fail miserably much of the time, but at least I feel guilty about it.  Recycling offers the opportunity to feel good about my environmental impact with little effort, since the garbage collection infrastructure in Portland makes recycling easy.

Some products are best extensively reprocessed before reused. Urine, as an example. There are proponents of topical and/or drinking urine as a treatment/cure for nearly any illnesses.  The kidneys are mostly responsible for fluid and electrolyte balance and I realize that normal urine is mostly water, salts, urea and a smattering of other very dilute molecules. I have the urine tox screen to prove it.  Urine is not a particularly noxious body fluid, but it is not high on my list of liquids to drink under normal circumstances.

Urine is mostly water but not an optimal source of water if it is your only source for fluids.  Urine drinkers love to mention the occasional trapped earthquake victim who survives, in part, from drinking their own urine.  For the first several days the urine would be dilute enough to keep people reasonably hydrated, as humans cannot concentrate urine as well as, say, a camel.  So I can see where consuming urine for a short period of time would delay progressive dehydration and death. A couple days of drinking urine neat, shaken not stirred, would be harmless and, if there were no alternative sources of water, beneficial. I do suffer from the societal taboo that piss is icky, and for aesthetic reasons urine is not something I would want to consume, even when it is referred to as its more common designation ‘Coors Light’.The kidney, I should mention, is the only organ in the body that functions on magic.  Really.  Does anyone actually believe/understand the function of the so called Loop of Henle?  I scoff at those who talk about human energy fields or water having memory, but as best I can tell, the Loop of Henle is no different.  My undergrad degree was in physics, so at some point I suppose I ‘understood’ quantum mechanics and relativity, at least well enough for the tests. The Loop? Bah. Total smoke and mirrors.

Drinking your own piss has a long history, especially in India and Asia and advocates (mis)quote the bible:

Proverbs 5:15. Drink water from your own cistern, running water from your own well.

Although the following verses suggest that it is a metaphor for marital fidelity, not consuming pee.  The bible has never been a convincing source of medical advice, although with teenage boys at home, I increasingly see the wisdom of Deuteronomy 21:18-21, Exodus 21:17 and Proverbs 30:17.

The rationale behind drinking your urine is simple: it is an ultrafiltrate of all that is best in the blood, with none of the toxins, which are processed and disposed of by the liver.  So when you drink your urine, you are consuming a golden elixir of salts, proteins, and hormones, containing all you need to treat virtually every disease and maintain health.  Sort of an uber-energy drink with none of the caffeine and fewer calories.  Your own, early morning, midstream urine is to be preferred, and in a pinch you could drink others urine, preferably from the same sex.  I suppose it would be wise to avoid the urine of  the autistic, it being loaded with mercury, aluminum, and perhaps other toxic metals.

Are there uses for urine? Popular culture has it that peeing on a jellyfish sting will relieve the pain; this is neither supported or denied by the Pubmeds.  It appears to be the one therapy with no supporting Cochrane review.  Urine on a jellyfish sting, if dilute, is counterproductive, since fresh water will trigger jellyfish nematocysts to fire and increase the pain of the sting.

Similarly, topical urine is advised for bee, mosquito and other venomous bites, with neither supporting or disconfirming data.  Given the medical benefits of urea (mostly as a moisturizer at concentrations many fold higher than in the urine) and other molecules in urine, they may be products in piss that would inactivate venomous stings.  I can’t dismiss the concept out of hand, although concentrations in  the urine of well hydrated people would be minimal. So use the urine from a trapped earthquake victim or lifeboat survivor,  which will become concentrated with time, and not your Corona addled swimming or hiking partner.

It is an ongoing curiosity how proponents of curious therapies will take a bit of truth an magnify its significance out of all proportion to reality. An example.

Urokinase is a protein that has utility in dissolving clots.   Its dose, depending on what is treated, is around 500,000 to 2 million units IV.  Normal urine contains urokinase, but how much?  ” Normal human urine contained 2068 ± 0.36 u/ml of UK”    Hardly enough to have any effects should it be consumed orally, especially given the ability to the gi tract to reduce any protein to amino acids.  Yet because urokinase is useful in high doses iv in patients with clot, it is also useful orally as a medicine. Odd logic.

One site notes there are 2 grams of protein and a 100 mg of glucose excreted the urine a day.  Is that lot?  A dollar bill weighs a gram and we make 1 to 2 liters of urine a day.  So a cup of urine will contain about half a dollar bill in weight of protein (roughly the same as a McDonalds meat patty) and 25 milligrams of glucose,  about as much as the “one” on the back of a dollar. Compare that to 8,000 milligrams of protein and 12,000 milligrams of glucose in a cup of milk. Not quite homeopathic concentrations, but close.

The arguments behind the use of medicinal piss are the usual: appeals to antiquity (not mentioning the average life expectancy of the ancients was just a tich longer than a fruit flies), innumerable anecdotes, and the ever popular secrets “they” don’t want you to know.

The medical community has already been aware of [urine's] astounding efficacy for decades, and yet none of us has ever been told about it. Why? Maybe they think it’s too controversial. Or maybe, more accurately, there wasn’t any monetary reward for telling people what scientists know about one of the most extraordinary natural healing elements in the world.”

It is getting increasingly difficult to keep track of all the miracle cures I am supposed to keep secret.  One of these days I am going to slip up and inadvertently cure someone with an effective and inexpensive natural remedy. Even dogs and monkeys participate in the healing effects of drinking their own urine.  Or they have sloppy aim.  Of course monkeys and dogs eat their own vomit, so I doubt they have a discerning palate.

My Loop of Henle psychosis not withstanding, the understanding of renal physiology by urinologists is, well, interesting.  One site calls urine “purer than distilled water” and then lists all the beneficial chemicals in the urine. Given that the purpose of distilled water is to make the product nothing but H20, it is an interesting contradiction.

or

Urine is believed to be a byproduct of blood filtration. It is NOT excess water that is released by the body. When blood filled with nutrients pass through the liver, the toxins are filtered out and are excreted as solid waste. The purified blood then travels to the kidney where excess nutrients are eliminated from the body.

George Carlin used to talk about ‘jumbo shrimp’ and ‘military intelligence’; perhaps we should add ‘CAM understanding’ to the list.

The problem is getting the nerve to drink your piss since there is an aversion to consuming pee. As Rita Mae Brown said in a different context, “Nothing is unnatural – just untried.” If you work yourself up to it, all things are possible:

How many people do you know who have drunk enough urine to really know what it tastes like? Probably not too many. Those who regularly drink their own urine say it. But taking urine into your mouth might be too big a step to begin with. Rubbing a drop into the and first smelling your own urine can help you to overcome part of the barrier. Really, it often does not smell bad at all. Many people even like its sometimes sweet odor. More extensive massaging of urine into your skin is also a good way to become accustomed to your life water. How can you overcome feelings of aversion to drinking your own golden elixir? Start by drinking a drop then a sip each day and slowly build up to a fill glass of urine. This is the most comfortable way to allow your body, mind and soul to become accustomed to this therapy.

I’ll pass.

It would seem for those who participate in urine therapy there is a certain embarrassment in talking about their life changing cure for everything.  It is kind of sad, really, and I feel for them.  It must be difficult to have easy access to the cure for all diseases and have to feel uncomfortable about discussing it due to societal taboos.  And if we meet in public, really, I don’t want to know if you drink piss. That would be, under almost every circumstance, the OED definition of over-sharing.

Urine therapy is, of course, a panacea.

…one of the most powerful, most researched and most medically proven natural cures ever discovered. Multiple sclerosis, colitis, lupus, rheumatoid arthritis, cancer, hepatitis, hyperactivity, pancreatic insufficiency, psoriasis, eczema, diabetes, herpes, mononucleosis, adrenal failure, allergies and so many other ailments have been relieved through use of this therapy

Not a bad list.  Looking on the interwebs, there is no medical condition that is not amenable to treatment with either topical or oral urine, and they wisely advise against intravenous injection.

Any evidence for efficacy?  Nope.  Just testimonials.
Any reason to suspect drinking your piss would help any medical condition?  No.  Given the dilute nature of the products in urine, it should be neither helpful nor harmful.

Of course, the lack of efficacy or plausibility is no hindrance to use.  As one web site on the mechanism of urine therapy notes

…theories have never been proven using modern scientific procedures to verify his ideas, and at some levels has been completely dis-proven, but nevertheless people still believe them. Maybe the power of belief in this instance overcomes what factually may not be real.

Sums up the whole field of alt med, does it not?

Addendum

The links to sources in this entry may or may not refer back to original sources.  As is often the case in the more marginal CAM therapies, many sites appear nearly identical in content, one large cut and paste fest. Even Vanderbilt University regurgitates the same text as if were original without proper references; one would think a University would be sensitive to issues of plagiarism,  although perhaps Vanderbilt is the original source.

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As we learned in Legislative Alchemy I: Naturopathy, legislative alchemy is the process used by state legislatures to transform implausible and unproven diagnostic methods and treatments into legal health care practices.

Today, we review how chiropractors are faring in the 2011 state legislative sessions.

Chiropractic 101

In 1895, a self-described “magnetic healer,” Daniel David Palmer, claimed to have discovered that every person possessed an “Innate Intelligence,” defined as the body’s capacity to heal itself, which flowed from the brain out through the nerves in the spinal cord. Misaligned vertebrae impinged on nerves and interfered with the flow of Innate Intelligence, causing “95 percent of all disease.”

Palmer named these putative misalignments “subluxations,” and began teaching students how to detect and correct them based on his notion that removing this interference would return the free flow of Innate Intelligence and the body would heal itself. In other words, chiropractic was — and, as we shall see, still is — simply another form of vitalism, a long-discredited notion that illnesses are caused by a disturbance or imbalance of the body’s “vital force,” which is distinct from the body’s biochemical processes.

Palmer and his disciples were arrested for practicing medicine without a license, which led to a strategy of chiropractors lobbying state legislatures for their own chiropractic practice acts. This effort stretched from 1913, when Kansas became the first state to license chiropractors, to 1974, when Louisiana became the last.

Subluxation: it’s the law

The non-existent chiropractic subluxation remains the central tenet of the 50 state chiropractic practice acts to this day.[1]

Twenty-one state chiropractic acts mention it specifically as the basis for chiropractic practice. For example, Connecticut defines chiropractic practice as:

the science of adjustment, manipulation and treatment of the human body in which vertebral subluxations and other malpositioned articulations and structures that may interfere with the normal generation, transmission and expression of nerve impulse between the brain, organs and tissue cells of the body, which may be a cause of the disease, are adjusted, manipulated or treated.

Twenty-three states refer to its purported attributes — without actually using the “s” word. In North Carolina, chiropractic practice is defined as:

the science of adjusting the cause of the disease by realigning the spine, releasing pressure on nerves radiating from the spine to all parts of the body, and allowing the nerves to carry their full quota of health current (nerve energy) from the brain to all parts of the body.

Did they say “science”? Here’s how much science is involved in chiropractic’s core concept — there’s not even a plausible hypothesis of what a subluxation is or how it might affect human functioning.

Six states simply incorporate by reference practices and procedures taught in chiropractic schools, which remain loyal to the subluxation although some have tried to distance themselves from the word, if not the concept.

This doesn’t mean, of course, that chiropractors are permitted by law to treat any disease or condition by detecting and correcting subluxations, just most any disease or condition, as long as the problem is defined in terms of the patient’s having one or more subluxations stopping up the “flow” of “nerve energy.” Asthma, allergies, ADHD, painful periods and earaches are a few of the many conditions widely advertised as treatable by chiropractic adjustment.

You might think it would cause the chiropractic industry some alarm that legislators might wake up to the fact that subluxations don’t exist. And apparently that is the case. In a few states chiropractors are attempting to expand the chiropractic scope of practice by including authority to prescribe that former anathema to chiropractic: drugs. For years chiropractors branded themselves as doctors who treat patients “without drugs or surgery.”

With drugs but not surgery

Chiropractic lobbying in New Mexico, the state where anyone can practice medicine, provides a perfect lesson in the insidious nature of CAM practitioner licensing. A few years ago, the state legislature invented a new iteration of chiropractor, the “certified advanced practice chiropractic physician.” With minimal training, this new type can, by statute, “prescribe, administer and dispense herbal medicines, homeopathic medicine, over-the-counter drugs, vitamins, minerals, enzymes, glandular products, protomorphogens, live cell products, gerovital, amino acids, dietary supplements, foods for special dietary use, bioidentical hormones, sterile water, sterile saline, sarapin or its generic, caffeine, procaine, oxygen , epinephrine and vapocoolants.”

Then, in 2009, the New Mexico legislature granted the state chiropractic board authority to develop a formulary for the “advanced practice chiropractic physician.” The requirement that substances be “natural or naturally derived” was eliminated, but there was a catch: “Dangerous drugs or controlled substances, drugs for administration by injection and substances not listed [in the quoted section, above] shall be submitted to the board of pharmacy and the New Mexico medical board for approval.”

Apparently, approval was not forthcoming to the chiropractors’ satisfaction, so they returned to the New Mexico legislature this year, seeking to dump the pharmacists and medical doctors. A new, improved version of the “advanced practice chiropractic physician” was proposed: one with a “prescription certificate.”

And just to make the point clear, the term “chiropractic” would be discarded from the New Mexico chiropractic practice act in favor of “chiropractic medicine.” Thus, the purpose of the practice act went from “granting chiropractors the right to practice chiropractic as taught and practiced in standard colleges of chiropractic” to granting “chiropractic physicians the right to practice chiropractic medicine …” [Emphasis added.]

Gone was the requirement of a pharmacy and medical board approved formulary. Instead, those with the “prescription certificate” would be authorized by statute to “prescribe, administer and dispense dangerous drugs, including compounded preparations for topical and oral administration and injection, testosterone in all its forms and codeine in cough syrup.” [Emphasis added.]

One can read between the lines thinking that goes something like: “If the pharmacists and medical doctors won’t let us prescribe testosterone ‘in all its forms’ and cough syrup with codeine, we’ll just put it in the statute and they can’t do a damn thing about it.”

Instead of pharmacy and medical board approval, the proposed legislation provided that “the [chiropractic] board, with the New Mexico Medical Board and the Board of Pharmacy serving in an advisory capacity, and with all parties agreeing to act in good faith, shall establish by rule a formulary …” [Emphasis added.]

Yeah! That’ll show ‘em!

Except the proposed legislation didn’t pass. It was still in committee when the legislature adjourned. New Mexico’s governor recently declared a special session of the legislature to deal with certain pressing problems, such as redistricting, and that has begun. We can only hope the chiropractors don’t try to shoehorn their bill into the special session agenda.

As a cautionary tale about the dangers of mission creep in “CAM” practitioner licensing, it is instructive to look at the education and training which would have been required of the “certified advanced practice chiropractic physician” in obtaining a “prescription certificate.”

In addition to the minimal requirements for “advanced practice” certification, the applicant must complete “pharmacological training from an institution of higher education approved by the [chiropractic] board or from a provider of continuing education approved by the board.” [Emphasis added.]

The applicant must complete a program, again approved by the chiropractic board, of 200 classroom hours in pharmacology, physiology, pathophysiology, physical and lab assessment and clinical pharmacotherapeutics, which, you’ll have to admit, is a really long word. Whether this is simply descriptive of, or in addition to, the education described in the previous paragraph is not clear. What is clear is that all of this can be accomplished within the current chiropractic educational system, a subject to which we will return in a future post.

But where, you might ask, would the chiropractor get experience actually treating patients with drugs, so essential to proper training? Well, remember those pesky medical doctors who were gumming up the formulary works? The ones the legislation sought to remove from the process? From them, that’s who.

In order to get the coveted “prescription certificate,” a chiropractor would have to complete 400 hours “of clinical rotation practicum in clinical assessment and pathophysiology” and 400 hours of 100 patients “with disorders relevant to the certified advanced practice chiropractic physician’s clinical specialty.” All done “under supervision of a medical doctor.”

One must wonder where one would find a medical doctor willing to take on supervision of a chiropractor treating patients with drugs.

A bad idea metastasizes

The chiropractic faction interested in foisting chiropractors as primary care physicians on the public was obviously not going to stop with New Mexico, and it didn’t.

In South Carolina, a bill would have created the same sort of “advanced practice chiropractic physician” as presently exists in New Mexico along with the option of obtaining a “prescription certificate” as proposed in the failed New Mexico legislation. The bill never made it out of the Senate Committee on Medical Affairs.

Likewise, in Alabama, a bill was introduced to allow prescription of “natural” compounds, “bio-identical hormones,” homeopathic remedies and other woo remedies favored by “CAM” practitioners. If the chiropractor took the same sort of 90-hour course as New Mexico allows, he or she could also prescribe and inject these substances even if they were classified as legend drugs. This bill also died in committee.

More scope of practice

Prescription authority was not the only means of increasing ways to make mon … I mean, increasing the scope of chiropractic practice attempted in this year’s legislative sessions.

In Illinois, lobbying efforts took a more subtle approach and attempted only an inclusion of authority to provide advice regarding the use of non-prescription products. Translation: they can advise patients regarding dietary supplements. And, of course, having given that advice, they can sell patients the supplements they’ve recommended. This bill, which also authorized chiropractors to administer atmospheric oxygen, made it into law. A bill in Hawaii, authorizing the use of “clinical nutritional methods” (whatever that means), died in committee.

Minnesota, another state where anyone can practice medicine, saw a failed attempt to include acupuncture within chiropractic scope of practice. Perhaps wary of attempts to make chiropractors actually go to acupuncture school and learn “real” acupuncture, this proposed legislation invented an entirely new form, defined as “a modality of treating abnormal physical conditions by stimulating various points of the body or interruption of the cutaneous integrity by needle insertion to secure a reflex relief of the symptoms by nerve stimulation as used as an adjunct to chiropractic adjustment.” Maybe they should have called it “acujustment”.

And on it goes

Last year, the Connecticut Board of Chiropractic Examiners issued a ruling that chiropractors need not warn patients of the risk of stroke following cervical manipulation, a ruling based largely on a study which specifically states it does not rule out such a risk.

In response, Connecticut Senator Len Fasano promised to introduce legislation in 2011 mandating a warning. Sen. Fasano testified at a hearing before the Board that he and others in the legislature were under the distinct impression the Board would indeed require this type of warning. Obviously, the Board did not do that, so Sen. Fasano kept his promise and introduced a bill requiring chiropractors to obtain informed written consent prior to any treatment of the cervical spine, including information on the risk of stroke. Unfortunately, the bill did not make it to the floor for a vote.

Finally, chiropractic lobbying in Florida screwed up passage of a perfectly good bill designed to protect the public’s health, safety and welfare.

A bill introduced to educate coaches, parents and young athletes about sports-related concussions and to require that an M.D. or D.O. sign off on return to play post-injury passed the House, where an attempt to include chiropractors was rebuffed in committee. However, the bill got bogged down in the Senate because of a similar attempt to force the inclusion of chiropractors in the type of health care practitioner with authority to clear the young athlete for continued play. The implication, of course, was that chiropractors were qualified to diagnose and treat traumatic brain injury, a conclusion not universally shared in the Senate, and rightly so. That squabble ran the clock out on what would have been a laudable safety measure for school athletes. And that’s a shame.

Conclusion

It is unfortunate enough that the state legislatures have legitimized a figment of the imagination first proposed by a charlatan in 1895 — the “subluxation” — by creating a licensed health care profession known as chiropractors to “detect” and “correct” them. Giving chiropractors authority to prescribe dietary supplements, and, even worse, drugs, only exacerbates their original mistake.  Instead of expanding the scope of practice, state legislatures should remove diagnosis and treatment of the nonexistent “subluxation” from the chiropractic practice acts.

References

1. Bellamy J., Legislative Alchemy: the US state chiropractic practice acts, Focus on Complementary and Alternative Therapies (2010)15(3): 214–222.

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