Herbal Remedies Can Interfere with HIV Treatment

The popularity of herbal remedies rests, in large part, on the perceptions of these substances as “natural,” a vague, nearly meaningless term often mistakenly understood to mean “safe.” The idea that eating parts of plants, singly or in combination, can have significant health benefits with little to no risk is one of the irrational cornerstones of alternative medicine. On the other hand, the idea that plants contain compounds which can have both beneficial and adverse health effects is a well-established and generally accepted fact. Herbal remedies very likely do have health benefits, we simply rarely have the data to identify these or the associated risks with enough certainty to justify claims made for them or clinical use of them.

Despite this, such remedies are not infrequently used by patients, often without the knowledge or guidance of healthcare professionals. Exactly how popular herbals are is unclear, but individual surveys suggest a small but significant number of patients use them. I recently ran across one such study, which illustrates the use of herbal remedies by human HIV patients and also sheds some light on the attitudes of such patients and on the potential risks of this behavior.

Vazquez Hernandez, M. Hurtado Gmez, MF. Blanco, JR. The influence of alternative medicine in highly active antiretroviral treatment. Farmacia Hospitalaria 2009;33(1):31-6.

Highly active antiretroviral treatment (HAART) is an approach which significantly reduces HIV morbidity and mortality and improves the quality and length of patient’s lives. While not a cure or devoid of side effects, it is a highly effective treatment that has had a tremendously positive impact on the well-being of people infected with HIV. As with most incurable conditions, however, there is a subpopulation of patients who are interested in alternative therapies to replace or augment conventional care. This study found 16.6% of the HIV patients surveyed used 1 or more presumably medicinal plants.

37.5% of these people thought of these plants as a form of medication, which is the appropriate perspective to take on herbal remedies, apart from the lack of evidence to document safety and efficacy for many of them. However, another 37.5% of the patients did not know medicinal plants could have any side effects, and none of the patients realized that these agents could interfere with the HAART that was so vital to their health. 62.5% of the patients did not know what the herbal remedy they were taking was, could not say what it was for, and were taking it on the advice of someone who was not a healthcare professional.

A variety of herbal agents were used, with grapefruit, milk thistle, and Echinacea being the most common. Though information about safety and possible interactions with pharmaceuticals is extremely limited for most herbal products (no literature was found for 54% of the agents used), some published evidence of negative effects of HAART was seen for 46% of the agents reported, including the three most common ones. The authors concluded:

Patients undergoing HAART regularly use medicinal plants and this often occurs without the knowledge of the doctor or pharmacist. There is evidence that herbal preparations can cause pharmacokinetic and pharmacodynamic interactions that represent a potential risk in patients undergoing HAART…

The population in general and the patients perceive these substances as healthy. The patients are not aware of the adverse effects that these can sometimes produce and that they can even cause HAART to fail. The reasons given for the consumption of medicinal plants is that the patients believe that these increase the efficacy of their treatment, improve their quality of life, reduce the adverse effects of HAART and give them a feeling of control.

This is a summary which probably applies equally well to many of groups of patients. Herbal remedies with significant but poorly understood physiologic effects can impact, both positively and negatively, the health of people who take them, but most people know little about what they are taking or why, do not understand that the benefits are unclear and that there are possible risks, and most rely on the advice of people other than their primary healthcare team. If herbal remedies are to find a place as effective medicines, we need to develop the research base to understand their effects and we need to educate patients and healthcare professionals about the potential risks and benefits and interactions with other therapies. This, of course, requires debunking the fallacy that such products are inherently safe because they are “natural.”

Posted in Herbs and Supplements | 1 Comment

Veterinary Stem Cells and Snake Oil

I have written several articles previously about veterinary stem cell therapies, which I view as a promising but as yet unproven treatment for a number of medical problems. (e.g. 1, 2, 3, 4, 5)  Though not “alternative” in origin, the marketing of these treatments and the arguments used to justify them in advance of adequate scientific data establishing safety and efficacy resembles the promotion of many alternative therapies.

I have received some pretty harsh criticism for suggesting this, so it was satisfying to read a recent editorial in the journal Veterinary Surgery:

Jeffery ND. Is ‘Stem Cell Therapy’ Becoming 21st Century Snake Oil? Veterinary Surgery 41 (2012) 189–19.

The author begins by cautioning us against “a non-critical acceptance of new advances because of a complacent assumption that previous mistakes regarding poor medical regulation will not be repeated in the modern world.” Obviously, this blog exists precisely because such mistakes, and reliance on prescientific methods of evaluating new ideas through personal experience, uncontrolled experimentation, and trust in authority, rather than reliance on rigorous controlled scientific research, are still widespread in our profession. As Dr. Jeffery correctly points out, the majority of veterinarians rightly deride pseudoscientific methods such as homeopathy (though too many still fall for it’s propaganda). And yet the same approaches to justifying other kinds of clinical interventions, both conventional and alternative, are all too common.

He then goes on to remind us that the promising preclinical research involving stem cell therapies does not justify their widespread clinical use without properly designed and conducted clinical trials. Most research on these therapies published so far has been methodologically inadequate to justify the burgeoning market in stem cells. However, the uncritical reports in the media of preclinical research, and the easy availability of testimonials and uncontrolled anecdotes about stem cell treatment, not to mention the aggressive marketing by stem cell therapy companies, make it “easy to sell to owners as a respectable treatment, even in the absence of rigorous proof of efficacy.”

Finally, Dr. Jeffery emphasizes something with which I conclude most of my own articles about unproven therapies, a call for a stricter standard in veterinary medicine for scientific evidence about our interventions.

Whilst stem cell therapy has rapidly achieved high profile in medicine and therefore even misplaced claims for efficacy are noteworthy it is not the only therapy in veterinary medicine or surgery for which there is insufficient evidence of benefit to support widespread implementation. Novel interventions for common conditions are published frequently in veterinary journals, including Veterinary Surgery. Whilst it is undoubtedly important that new interventions are explained through publication, it is essential that they should subsequently be subject to critical testing of their effectiveness before being widely accepted. This is currently not standard practice in veterinary medicine and surgery… Strict testing of novel interventions must become the norm for veterinarians to be able to maintain our view of ourselves as a ‘science-led’ profession.

I couldn’t agree more.

Posted in General | 8 Comments

Garlic for Pets- What’s it Good for?

One of the most popular plant products touted for medicinal use in pets is garlic Allium sativum. A recent newsletter by Dr. Deva Khalsa, a popular alternative veterinarian, makes some typical claims:

Garlic is a miracle herb!

Garlic (Allium sativum) has been valued for thousands of years for medicinal purposes.

reported adverse affects from garlic add up to a total non-event over the past 22 years….This proves beyond the shadow of a doubt that the risk of using garlic is so infintessimally low that it’s simply statistically insignificant. What is significant is all the positive research delineating the medicinal powers of garlic.

a natural antibioitic

it’s antifungal, antiviral and antibacterial effects can contribute to the healing process.

Garlic increases general immune activity

Uncooked garlic helps to lower blood triglycerides and choleterol making it useful for certain breeds (Schnauzers and Beagles) that are predisposed to this problem.

Compounds in garlic act as antioxidants and help flush toxins out.

garlic has been fed to dogs in order to help prevent flea infestation.

A host of studies provide evidence that the allicin in garlic works to inhibit cancer formation.

Since these pretty fairly represent the claims made for garlic, I will address each in turn.

1. Garlic is a miracle herb-
Well, miracle is a pretty tough word to justify when applied to any medical therapy, all of which come with pros and cons. I’d call this a warning sign!

2. Garlic has been used medicinally for thousands of years.
True, but irrelevant to whether or not it works. The traditional use of plants as medicines has a poor record of predicting uses that are actually proven valid by controlled scientific testing. Here are some of the traditional uses record for garlic (from Wynn SG. Fougere BJ. (2007). Veterinary Herbal Medicine St. Louis: Mosby Elsevier.)

Traditionally, garlic has been used in humans [or animals] for abnormal growths, bronchitis, pneumonia, digestive problems, intestinal infection, tuberculosis, dysentery, earache and ear infection, vascular disorders…influenza…relieve toxicities, and kill parasites…treatment of a cow that was unable to rise after calving…coccidiosis in poultry…breast tumors on dogs (topically), for distemper, for jaundice, for rheumatism, and for thyroid complaints and worms…for fungal infection and swelling of the tongue, oral blisters and wounds…contagious abortion, tetanus, milky diarrhea, abdominal pain, asthma, polyuria, sores, compound fractures, epilepsy and swelling of the kidneys, gangrene of the lung…

When something is used to treat such a wide variety of apparently unrelated medical conditions, either it is a miracle or it is an example of how easily people can be fooled into thinking a useless therapy is helping. A truly miraculous therapy shouldn’t have any trouble proving itself in scientific testing, so when the evidence is lacking despite centuries of use and decades of research, the most likely explanation is human fallibility rather than miracle cure.

3. Risk of using garlic is negligible.
Mostly true. A number of in vitro and lab animal studies have shown the potential for garlic to cause anemia and other problems. Studies looking at garlic as a potential antimicrobial in swine feed found the pigs ate less and gained less weight (and also had and “objectionable” taste, for those carnivores among you). However, the amount of garlic which must be fed to cause clinical illness in dogs is probably much larger than is typically used. Cats are much more sensitive, but they are also less likely to accept garlic.

There are a couple of important caveats here, though. For one thing, the in vitro and lab animal studies showing potential dangers of garlic, which Dr. Deva and other proponents of garlic dismiss as not relevant to actual use, are exactly the same kinds of studies which show potential benefits and which they constantly cite to justify actual use of garlic. This is a classic case of confirmation bias in which people accept as valid evidence which supports their position but reject evidence which contradicts it.

The other factor is that there are case reports of individual dogs who experienced anemia, high blood pressure, and other serious adverse effects from consuming relatively small amounts of garlic (e.g. 1, 2). It is often the case with pharmaceuticals, which appear safe in relatively small test populations of a few thousand people, less common sensitivities in some individuals appear when they are given to much larger numbers of patients. This is part of the business of balancing the risks and benefits of any treatment. So while the risks of garlic appear to be low for most dogs, it is not appropriate to assume they are inconsequential, especially when evidence for benefits is so poor (as we will see).

4. Garlic has antibiotic, antifungal, and anti-parasitic properties.
Maybe. The basis of this claim, apart from low-reliability evidence such as anecdote and opinion, is in in vitro and animal model studies. Chemicals from garlic do have effects on bacteria, fungi, and parasitic organisms in the laboratory. This only suggests that these chemicals might have similar effects in the real world. It doesn’t prove anything. What an isolated chemical does in a petri dish is not necessarily what feeding garlic will do in a living animal. And as I often remind people, bleach has antibiotic, antifungal, and anti-parasitic properties in the lab, but I wouldn’t recommend it as a dietary supplement!

The research in real animals is mixed. Garlic has failed to show benefit in at least as many studies as it has shown some effects, so the balance of the evidence is unclear. And the published research is almost all in agricultural animals, not companion animals.

5. Garlic “boosts” the immune system.
Nonsense. The notion of a general immune stimulant which has clinically beneficial effects and no side effects is a fantasy that ignores the incredible complexity of the immune system and how it interacts with all the potential threats it is exposed to. This empty bit of marketing is discussed, and demolished, in detail in this article.

6. Garlic lowers triglycerides and cholesterol.
Probably not. A 2009 review of the research in humans found that “the available evidence from randomized controlled trial does not demonstrate any beneficial effects of garlic on serum cholesterol.” The point is largely moot since blood lipids are almost never a meaningful health issue in companion animal species. It is true, as Dr. Deva suggests, that it is an uncommon problem in certain breeds. However, I would note that both of the dogs in the case reports I mentioned before who suffered harm from eating garlic were Schnauzers, the same breed that most often exhibits this otherwise rare problem. So I’d be very careful about suggesting garlic as a remedy for this issue in this breed given the lack of evidence for a benefit and the presence of evidence for possible risk.

7. Garlic is an anti-oxidant and helps remove “toxins”
A hypothetical treatment for a hypothetical problem. First off, the subject of oxidation and anti-oxidants is about as complex as the subject of immune system activation, and there is growing evidence that anti-oxidant therapies do little good and some harm (e.g. 3, 4, 5). So while garlic compounds show some antioxidant properties in the lab, they also show the ability to cause oxidative damage (that’s where the anemia comes from), and there is zero evidence in real cats and dogs for any benefit from garlic as an anti-oxidant.

Secondly, the mysterious “toxins” so often mentioned as a target for health promoting therapies are a classic sign of snake oil marketing. Without information about specific toxins, evidence for the harm they do, information about how they are processed and eliminated by the body, and evidence concerning how garlic can aid in this process, this claim is totally meaningless. And, not surprisingly, none of the information or evidence is offered for garlic.

8. Garlic is an effective flea control method.
Doubtful. There are, of course, plenty of anecdotes from people saying that garlic drove the fleas away from their pets like magic. There are just as many that say garlic didn’t help at all. There is absolutely no research evidence showing garlic supplements to be an effective form of flea control. It is often given with Brewer’s yeast, which has been shown to be ineffective as a flea repellant. So for all the confidence with which this claim is made, it is simply made up.

9. Garlic is useful in prevention or treatment of cancer.
Maybe. There is low to medium level evidence in humans that eating garlic may reduce the risk of some kinds of cancer. The American Cancer Society concludes

there is not enough evidence at this time to support eating large amounts of garlic or taking garlic supplements for cancer prevention. Garlic may have the potential to interfere with anesthesia or other medicines. It is reasonable to include garlic as part of a balanced diet, unless one has a particular health problem or is taking medication that has been shown to be adversely affected by garlic.

Other research summaries show a mix of possible benefits and risks, including bleeding and interference with the action of a number of medicine. So like anything with the potential for benefit, there is the potential for harm.

And, as usual, none of this research has been done in companion animal species. So while extrapolation from research in humans is often necessary, it is also a great way to draw the wrong conclusions. Such research strongly suggests which ideas may be worth pursuing and which may not, but it certainly doesn’t provide a confident, reliable answer about what to do for our pets.

Bottom Line
In vitro and lab animal research suggests a number of potential uses for garlic. The same level of research suggests some potential danger to garlic use in dogs and cats. There is almost no clinical research to substantiate any of the claims made for garlic use in pets. Traditional use suggests almost every pant is a cure-all, and the majority of such claims have yet to pass the test of scientific study. So at this point, hysterical claims of garlic as a “miracle food” are totally unjustified. The potential benefits deserve to be investigated, but they are mostly theoretical and unproven. The risks are probably low overall, but some individuals have been harmed by eating garlic, and we are currently unable to predict accurately which patients will be adversely affected.

Posted in Herbs and Supplements | 20 Comments

Funny for Some of You

(From Veterinarians Behaving Badly. Hasn’t happened to me yet, but I’ve been taken to task, and others I know have been banned for expressing their critical thinking)

Posted in Humor | 10 Comments

Misleading Advertising for Raw Pet Food (again)

H.G. Wells is credited with saying, “Advertising is legalized lying,” though I cannot imagine he is the first person to have thought so. Of course, the difficulty with identifying actual lying in advertising is that it is impossible to know whether the person making false claims actually believes their statements are true. When talking about inaccurate advertising of alternative medicine, supplements, unconventional diets, or even conventional therapies such as stem cell injections, I try to make the safer and more charitable assumption that the advertiser believes what they are saying, however egregiously implausible and inaccurate it may be.

Unfortunately, whether inaccurate claims made to sell a product are genuine misconceptions or deliberate deception, the truthfulness of the claims is often not something the consumer can judge, so false claims sell just as effectively as the truth. And because of the undeniable effectiveness of science as a means of identifying the truth, claims of “scientifically proven” benefits are often made in advertising healthcare products and services, which creates an undeserved and false appearance of legitimacy to unsupported, pseudoscientific ideas.

The latest example I have run across of this phenomenon, and a particularly brazen one, is the advertising of Souly’s Raw Pet Food. I’ve written in detail about raw diets before, and the bottom line is that there is no reliable research to indicate any benefits at all to feeding our pets raw food. The theories behind these diets are a mixture of reasonable supposition and nonsense, but there is no sound evidence to support any of them. There is, however, abundant evidence that cooked food is more nutritious than raw food, and that raw diets come with serious risks, including nutritional inadequacy and contamination with harmful bacteria. Despite this lack of any real reason to believe raw diets are good for our pets, manufacturers and promoters of these diets are not shy of making aggressive claims.

A press release from the makers of Souly’s sounds like a report on a new scientific study, but a close reading finds no evidence of any research at all, merely unsupported opinion and error.

Soul’y Raw Pet Food Discovers that Switching Your Pet to a 100% Handmade Raw Food Diet has been Successful as an Alternative Treatment for Coprophagia

The most common cause [of coprophagia] is usually a dog that is lacking a diet that provides him with sufficient vitamins and minerals to quell the desire to seek out other food sources to make up for the deficiency….Soul’y Raw Pet Food in San Marcos CA has noticed that the practice of dogs consuming their own feces or that of other dogs has all together stopped in their loveable following of furry friends when transitioned to their high quality raw food diet. One could say that this simple breakthrough in successfully deterring pets from seeking out feces as an alternative food source is just what the Doctor ordered.

To begin with, the consensus among veterinary nutritionists is that medical and nutritional causes of coprophagia are quite rare. It is usually behavioral in origin and can be a normal activity for healthy dogs and cats. The claim that it is the result of a nutritional deficiency is not supported by any evidence, and the implication that a raw diet would prevent such a deficiency better than conventional commercial diets is even more preposterous. And in this case, the “evidence” appears to be nothing more than the opinions and observations of the diet manufacturer and their friends, which hardly merits a press release announcing a scientific “breakthrough.”

But further reading clearly illustrates that the folks at Soul’y Raw Pet Diets do not understand nutritional science and care little about what scientific evidence supports or doesn’t support.

Soul’y Raw Pet Food does not chemically alter any of our ingredients by cooking or any other manufacturing process. Research has shown that most pet food allergies are derived from denaturing the ingredients and their bodies are not able to recognize them as a protein and their bodies will try to fight off the foreign body which creates the chronic allergic reactions.

This explanation is, in fact, the exact opposite of the true nature of dietary allergies. Whole proteins are the primary trigger for allergies in animals predisposed to have them. And when there is a malfunction in the GI tract such that it fails to break proteins down into small enough pieces, this can make allergies more likely. Finally, one of the most effective treatments for food allergies is to feed hydrolyzed protein diets, diets in which the proteins are chemically processed (gasp!) into small enough pieces that they cannot trigger an allergy reaction.

I certainly don’t expect lay people to be experts in the mechanics of digestion and food allergies, but this level of ignorance is frightening and inexcusable in a manufacturer of a pet food. It also indicates the blatant disregard for scientific fact so often seen in the marketing and promotion of raw and other unconventional pet diets.

The company’s web site contains many other examples of unproven or simply incorrect assertions. Their diet is claimed to be “PROVEN” to control allergies, though there is no research to support this. The company also claims eating their diet will prevent lawn staining, reduce vet bills through the ever-popular “strengthening the immune system” nonsense, and even prevent flea infestation! These are all implausible claims presented with no real evidence.

Finally,  the terms “human grade” and “restaurant grade” are frequently used for the ingredients despite the fact that these are not legally defined terms or part of the USDA meat grading system. Use of such meaningless terms cannot be anything but misleading and deceptive since they appear to indicate an official judgment on the quality of the food’s ingredients when the manufacturers must know that no such judgment has been made by anyone but them.

My purpose is not to pick on a single manufacturer, though the advertising by this company is certainly inaccurate and misleading. The unfortunate truth is that advertising full of unproven claims and inaccuracies is widespread in the marketing of veterinary health products. A blithe disregard for the meaning of the term “scientifically proven,” as shown by using this term and others like “research proves” and “studies show” without citing any actual published scientific studies, is a warning sign for the consumer. Such terms are meaningless at best and a signs of active deception at worst.

The best chance for us to identify what is truly beneficial for our pets is not to rely on advertising but to demand claims be supported by actual scientific evidence. Where such evidence doesn’t exist, claims that the benefits of a product are “proven” should be regarded as deceptive. The most that should be said in the absence of true scientific evidence  is that a product might have benefits and that some people believe they have seen it work. The same, of course, has been said of every health practice ever invented, whether it worked or not, so this is not a very reliable guide to the truth of such claims, but at least it is not actively misleading.

 

Posted in Nutrition | 11 Comments

EBVMA Symposium 2012– Evidence-Based Veterinary Medicine: It’s Happening Now!

This is the only event, and the only organization, dedicated entirely to promoting evidence-based veterinary medicine, and I encourage anyone interested to join us in New Orleans!

When: Wednesday May 30, 2012, 9am-5pm (One day before the start of the ACVIM Forum, one of the most popular CE events of the year!)

Where: Springfield Suites Marriott Downtown, New Orleans, LA

Program An Introduction to Evidence-Based Veterinary Medicine This interactive workshop, led by some of the leading teachers and practitioners in the field, will introduce you to the key concepts and methods of evidence-based veterinary medicine.

The Latest in Applied Evidence-Based Veterinary Medicine A series of lectures discussing recent research and practical application of evidence-based medicine methods, including the latest Veterinary Emergency & Critical Care guidelines for CPR, research reporting guidelines, outcomes assessment tools, and more. Speakers include Dr. Daniel Fletcher (Cornell), Dr. Paul Morley (CSU), and Dr. Sandi Lefebvre (Banfield).

Registration Morning Workshop (9am-12pm)- $50 (students $25) Afternoon Lectures (1pm-5pm)- $50 (students $25) EBVMA Business Meeting for members (5pm-7pm)- no charge

Combined all-day registration (includes 1-year EBVMA membership for first-time members)- $75 (students $40)

Late Registration (after April 15)- $65 each session ($40 students), $100 combined (students $65)

Details and Online Registration at www.ebvma.org

 

Posted in General | 2 Comments

Verm-X Herbal Parasite Control: No Real Evidence to Show it is Safe or Effective

I was recently asked by a reader to take a look at a product that had been recommended for deworming their dog, Verm-X. Unfortunately, there is little I can say about this product since, as is all too often the case, the manufacturer manages to make a good living selling it without having to generate any scientific information about the effectiveness or safety of the product. There are, as usual, many classic signs of snake oil:

Broad claims of efficacy and safety given without evidence.

A “kitchen sink” combination of ingredients with no research evidence on the combination and little to no evidence supporting use of the individual components.

Vague references to scientific validation with no actual published studies.

Reliance on testimonials to convince potential customers.

What Is It?
The company web site lists the ingredients for the dog product as:

Ingredients include: Allum sativum [garlic, should be allium];

Cinnamomum zelandicum [cinnamon, should be zeylanicum]

Mentha piperita [peppermint]

Thymus vulgaris [thyme]

Galium aperine [herb with various names]

Capsicum minimum [cayenne pepper]

Brown Rice, Poultry Meal, Refined Chicken Fat, Beet Pulp, Potato, Potato Starch, Verm-X Canine Blend, Brewers Yeast, Chicken Liver, Salmon Oil, Seaweed, Green Tea Extract, Prebiotic FOS, Prebiotic MOS, Minerals and Vitamins.

Though I haven’t gone through every one of their products, the herbal components appear to be the same for all species, with some differences in the other ingredients (flavors, vitamins, etc)

Does It Work?
As is so often the case with these unregulated concoctions, the bottom line answer is “who knows?” Apart from the garlic, which has been demonstrated to be ineffective as a flea control product and can cause an oxidative anemia in dogs and cats, I was able to find no published evidence concerning the safety and effectiveness of these ingredients, nor the combination, as parasite control. One of the company sites does say, “ Successful trials at Plumpton College, West Sussex have been carried out on its action as repellent of internal parasites.” I have not been able to locate any such studies in any directory of published research or on the company sites.

As usual with such products, the absence of evidence probably is evidence of absence, since any convincing scientific research support would be an invaluable marketing tool. The company has been fined in New Zealand for unsupported medical claims about its product, but enforcement of what little regulation there is for veterinary herbal products in the U.S. is virtually non-existent, so no proof of any sort is likely to be required here.

Bottom Line
With a hodgepodge of unproven herbal ingredients, no apparent research evidence to show the product is safe or effective, and a number of warning signs, I would not recommend this product. Available conventional parasite products have abundant research evidence of safety and efficacy and are a better choice.

Posted in Herbs and Supplements | 7 Comments

Book Review: Lessons from the History of Medical Delusions

A brief reference on the web site The Quackometer recently drew my attention to a very short book (really more of a pamphlet, in the historical sense) by Dr. Worthington Hooker, Lessons from the History of Medical Delusions, which I thought might be of interest to readers of this blog. Though published in 1850, the book contains many eloquent observations that are just as relevant to understanding how pseudoscience and quackery persist and even flourish in what we otherwise assume to be an age of scientific medicine. The book is available online as a Google eBook, and relatively cheap printed facsimiles are available as well.

Dr. Hooker was a physician, a professor at Yale, and an outspoken critic of homeopathy in it’s early days. His critique of homeopathy still resonates today, and has long drawn the ire of Hahneman loyalists, such as this one who makes reference to Dr. Hooker’s, “periodical fulminations for the destruction of Homoeopathy that have appeared like locusts or cholera at certain dates.” Though Dr. Hooker wrote an entire book discussing homeopathy, Homeopathy: An Examination of its Doctrines and Evidences, he does spare a few words here for this less-than-venerated practice:

The error I have been illustrating is carried to an extreme by the Homeopathist. He attributes palpable results to doses of medicine which are so small that they cannot produce any perceptible effect except by miracle.

He also includes a lengthy and preposterous example of a homeopathic proving, taken from a homeopathic text of the time,  illustrating the absurdity of simply listing every imaginable (and imagined) experience following the taking of a substance and then attributing the entire list to that substance in order to guide the selection and use of homeopathic remedies. However, the focus of this booklet is to illustrate more generally the sorts of errors in thinking that lead even otherwise intelligent and reasonable people to believe such nonsense.

And Hooker  makes a specific point of reminding us that belief in medical absurdities is not by any means a characteristic only of the unintelligent, the uneducated or the past.

The history of medical delusions most copiously illustrates the truth, that folly is very far from being confined to fools.

The present generation laugh at the follies of the past but have quite as great follies of their own, an follies too of a similar character, and products of the same fundamental errors.

The majority [of believers in quackery] is made up of those who are more or less intelligent and rational on most subjects, but who…are especially deluded on the subject of medicine…The exposition I make is not a partial one. It is not a one-sided argument-a plea for the doctors against the people. But it is an attempt to show how both doctors and people have ever been liable to error, and how they have been alike in the common elements, if not in the forms and modes and fashions of their delusions.

The medical profession, like the community at large, is made up of fallible men, and the elements of delusion are the same in the one class as in the other [though] the error of the physician would be refined, and would have the pomp and circumstance of erudition.

Error gilded with the pomp and circumstance of erudition….That certainly brings a few names to mind, eh?

Some of the specific examples he uses are fine tidbits of historical minutia. Apparently, one of the founding fathers of chemistry, Robert Boyle, also expressed his belief that dysentery could be cured through use of the thighbone of an executed criminal. And according to Hooker, Francis Bacon, that luminary of critical thinking and scientific philosophy, advocated for applying healing salves to the weapon that made a wound rather than the wound itself (though given the loathsome nature of many therapeutic unguents of the time, this may not have been a bad idea since apply them to wounds doesn’t sound wise).

So what are the common “elements of delusion” that Hooker wishes to warn us of? He begins with the post hoc ergo propter hoc fallacy.

The first [element] which I shall notice is the too ready disposition to consider whatever follows as a cause as being the result of that cause.

He then points out the most obvious reason why this sort of reasoning so often misleads us in medicine:

The most important of the confounding causes is “vis medicatrix naturae, or the tendency there is in the system to remove disease and cure itself….there is in the system a tendency to spontaneous restoration in case of injury and disease…This tendency is the chief agency in most cases in curing disease. Sometimes it is the only one; and very often it effects a cure in spite of the mistaken and officious interference of art.

And yet quacks, and even physicians, and the public generally, are very prone to leave this agency out of view, and to attribute cures, as a matter of course, entirely to some favorite remedy which has been used. This disposition is the chief source of medical errors of all classes of men.

Hooker also touches on several other key sources of erroneous conclusions in evaluating medical theories, including confirmation bias, availability bias, anchoring, premature closure, sloppy use of analogous reasoning, passionate commitment to theories without empirical evidence, and medical fads, though all describe in a language rather more poetic than we would ordinarily use today.

He then goes on to talk about the issue of the commercial and political success of medical nonsense, which are certainly still relevant issues often discussed here.

So extensive is the popular delusion in regard to quack medicines, that the nostrum system has become an organized system, with an enormous machinery of certificates and advertisements. It has become a monstrous business interest, and is linked in with a thousand ties with other business interests. So powerful is it in this respect, that it has almost entirely subsidized the press, forcing it to be silent except when it speaks in it’s favor. The same may be substantially said when speaking of the action of legislatures on this subject.

Similarly, Hooker touches on the unfortunate aura of legitimacy that attaches to quack therapies when they are embraced by what he calls “medical men in good standing,” which could certainly be applied to the quackademic medicine phenomenon and the endorsement of medical nonsense by the likes of Dr. Oz and others.

Despite the eloquent expression of many issues associated with medical nonsense that are as relevant today as they were in 1850, not all of Dr. Hooker’s book will resonate with a modern audience. Apart from the florid prose style of the time, and the unabashedly sexist language, he scoffs a bit “the skeptic,” who he describes as sitting in “his ‘doubting castle’ well-fortified against all the shafts of truth.” He also was a fan of bloodletting as a remedy, and sneered at the research of Pierre Charles Alexandre Louis and others who demonstrated its lack of effect. In general, he was no fan of the “numerical” methods which have since developed into epidemiology, and he was overly respectful of the experience and judgment on individual doctors. Citing the same sloppy reasoning as is often used by modern proponents of alternative therapies, he argues that such “numerical observations…can be of no practical use to the physician in deciding in regard to any individual case…”

However, as a whole this little historical gem is strikingly applicable to the issues this blog deals with today. And it ends with a nice description of the gradual and imperfect process of vetting ideas through scientific inquiry, from initial unjustified enthusiasm to a gradual withering of bad ideas and a fitting of good ones into their appropriate but limited places.

While many remedies, once potent to cure in the public estimation, have….been wholly discarded, others, which have more real merit, while they have lost the extravagant reputation of their nascent state, have, under the watchful eye of experience, gradually obtained very nearly their right valuation, and the circumstances which should regulate their use have been ascertained with considerable accuracy. Others, in great numbers, are now going through this searching process; and others still are just now wearing the brilliant honors of an enthusiastic reception.

He also suggests, mistakenly I hope, that direct attacks on medical nonsense rarely have a salutary impact on the popularity of such practices. However, he also describes with some hopefulness the goal of his book, which I think to some extent describes the purpose of this blog as well.

No delusion however fiercely it may have been attacked was ever killed. Each after having withstood all assaults, has laid itself down o die in the most quiet manner, benumbed into the sleep of death by the chill of popular neglect, while the warm breeze of popular favor which it once enjoyed are now bestowed upon some other delusion…

And such exposition as this essay presents, of the common causes of medical delusion, both in the profession and in the community, will, I believe, commend itself to the reason and common sense of such persons, and will therefore have some influence, in connection with other kindred efforts, in deterring them from giving heir patronage to quackery in any form…

 

 

Posted in Book Reviews | 2 Comments

Acupuncture vs Opioids for Surgical Pain in Dogs: Which is Better?

My attention was recently drawn to a veterinary acupuncture study which appears, superficially, to show acupuncture to be equivalent to opioid analgesia for post-operative pain in dogs. Unfortunately, especially for the research subjects, the design of the study was deeply flawed, and the conclusions the data support are far weaker.

D. Groppetti, A. M. Pecile, P. Sacerdote, V. Bronzo and G. Ravasio. Effectiveness of electroacupuncture analgesia compared with opioid administration in a dog model: a pilot study. British Journal of Anaesthesia 107 (4): 612–18 (2011).

What They Did
The investigators randomly assigned six healthy dogs to each of two groups. One group was sedated with the anesthetic propofol while needles were inserted into purported acupuncture points as determined by Traditional Chinese Medicine (TCM) principles. (Which is a bit misleading since traditional acupuncture was applied only to humans and the translation of the principles to dogs is a modern invention of the West). After 40 min of intermittent stimulation of these needles with electrical current, the animals were fully anesthetized and surgically neutered.

The other group was also sedated with propofol for the same period of time and also received the narcotic pain medication butorphanol at a dose of 0.2mg/kg 15 minutes before surgery.

The surgery was done routinely (though the average length of time in surgery was about 35min for both groups, which is about twice as long as the procedure typically takes an experienced surgeon. Such studies often involve surgery by veterinary students, but it is not clear from the paper who performed the operations in these subjects). The dogs were monitored and assessed up to 24 hours after surgery for signs of pain according to a subjective pain scale by observers blinded to the treatment category. Heart rate, respiratory rate, and amount of anesthetic gas needed to keep patients asleep during the surgery were measured and compared between groups. Measurements of a chemical in the blood called beta endorphin were also taken from the beginning of the procedure until 24 hours after surgery.

What They Found
There was no difference in the objective measurements of heart rate and respiratory rate during the surgery between the two groups. There was a difference in the more subjective measurement of amount of anesthetic gas needed to keep the patient at a proper plane of anesthesia, but this difference was significant at only 1 of 5 points measured.

The beta endorphin levels measured were highly variable, and differed significantly between the two groups at only 2 of 10 points measured, the end of surgery and 3 hours after surgery.

Subjective pain scores were higher for the control group than for the acupuncture group at all points measured, and this difference was significant at 12 of 14 points measured, continuously from 30min after surgery until 10 hours after surgery.

None of the dogs in the acupuncture group required additional pain medication as determined by pain score, but 4 of 6 dogs in the control group did.

No apparent side-effects were seen in the opioid group, but interestingly 4 of 6 dogs in the acupuncture group vomited after surgery.

Major Problems
There are serious problems with this study, and these undermine the conclusions of the authors that the study, “ demonstrated the ability of electroacupuncture to decrease anaesthetic and analgesic requirements in dogs during and after surgical neutering.”

1. Was the intervention studied actually acupuncture?
Obviously, electrical stimulation of needles in the skin is not a traditional Chinese therapy dating back thousands of years. Apart from the selection of locations for the needles, it bears less resemblance to TCM than to TENS, Transcutaneous Electrical Nerve Stimulation. This is a conventional therapy dating from about the 1970s that has reasonably good evidence of benefit for post-surgical pain, and which appears to work, at least partly, through general stimulation of opioid pain receptors via beta endorphin.

One could argue that despite the use of electrical stimulation, this intervention counts as acupuncture because traditional TCM principles dictated where the electrodes were placed. However, extensive evidence shows that sham acupuncture, involving placing needles in random locations or even not piercing the skin at all, is just as effective for pain as using traditional TCM acupuncture points. The authors of this study even stipulate this when explaining why no sham acupuncture control was included:

In clinical trials, sham acupuncture is considered necessary to demonstrate how a treatment is effective. However, it was argued that every penetration of a needle through the skin, be it at an acupuncture point or not, produces physiological effects, partly due to activation of a pain-suppressing system in the spinal cord (diffuse noxious inhibitory controls).

So if TENS achieves pain control through non-specific activation of opioid receptors via beta endorphin by electrical stimulation of the skin regardless of the location, and if the intervention in this study consisted of achieving pain control through non-specific activation of opioid receptors via beta endorphin by electrical stimulation of the skin, and the effect did not depend on the location of needle placement, in what sense is this “acupuncture” at all rather than TENS? How does it validate the principles or practices of TCM?

2. Butorphanol Sucks!
The choice of comparator was wholly inappropriate in this study. Butorphanol is widely recognized as a weak analgesic inadequate to control surgical pain. Numerous studies have shown it to be weak and to have a duration of action of 20-45minutes (1-3). In one study, butorphanol was statistically no better than placebo as an analgesic.

In this study, a low dose of the butorphanol was given 15 minutes before surgery. This would likely have provided limited pain control, and would have worn off by the end of the 35-minute procedure. So the control dogs had weak analgesia during the procedure and essentially none afterwards. Apart from the fact that this choice of comparison can only serve to make the test intervention look far better than it would compared to effective, standard-of-care pain control, it seems a questionable ethical choice given the clear evidence that butorphanol is not an adequate analgesic for this sort of procedure. Fortunately, at least the dogs were given rescue analgesia with more effective drugs when the pain scale seemed to indicate it was necessary.

3. Statistics
Though it is not clear from the paper, and is a less significant problem, the authors made multiple statistical comparisons, and there is no indication of whether or not they adjusted the level of statistical significance to account for this. This is perhaps the most common statistical error in the veterinary literature. Given the small numbers of subjects in the two groups, such an error could easily create the impression of difference greater than chance where non actually exist.

What Does it Really Mean?
This paper confirms the conclusion supported by much prior research: sticking needles into the skin and running electrical current through them results in a non-specific response that elevates beta endorphin levels and can suppress pain. The same phenomenon occurs with any trauma, so one could conceivably suppress post-surgical pain by banging on the patient’s toe with a hammer. While the effects of TENS has real potential value for pain control, it has nothing to do with the traditional theoretical constructs of TCM or acupuncture, and it is misleading to refer to it as “electroacupuncture” at all.

During the time the butorphanol would be expected to be active (while the dogs were anesthetized and undergoing surgery), there were no differences in objective measures that one would expect to reflect pain, such as heart rate and respiratory rate. So the electrical simulation appears to have been as effective as the lousy opioid analgesic while the dogs were anesthetized. Similarly, there were few significant differences in beta endorphin levels between the groups (or possibly none, depending on the appropriateness of the statistical methods), which suggests that the “trauma” of the needle insertion and stimulation had only a modest non-specific effect on the opioid receptor system. Since the butorphanol likely had worn off by the end of the surgery, this small effect was clearly better than complete lack of analgesic therapy the control dogs received. But this is hardly relevant to a patient population treated properly with effective, multimodal analgesia. And given that most of the dogs in the treatment group experienced post-operative vomiting, likely due to the stimulation of the opioid receptor system, it cannot even be argued that this approach lacks significant side effects.

If the conclusions of this paper had been limited to those justified by the data, the study would be a useful bit of data to consider in investigating the role of TENS in post-operative pain control. Unfortunately, the title, abstract, and discussion sections all create the unjustified impression that somehow TCM and traditional acupuncture are as effective as opioid analgesics in controlling post-operative pain, or perhaps even better. This will only perpetuate the myths and misunderstanding surrounding acupuncture and encourage the use of traditional practices that have not, in fact, been shown to be appropriate for this purpose.

References
1. K A Grimm; W J Tranquilli; J C Thurmon; G J Benson.Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs Am J Vet Res. January 2000;61(1):42-7.

2. K A Mathews; G Pettifer; R Foster; W McDonell. Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. Am J Vet Res. June 2001;62(6):882-8.

3. D C Sawyer1; R H Rech; R A Durham; T Adams; M A Richter; E L Striler. Dose response to butorphanol administered subcutaneously to increase visceral nociceptive threshold in dogs. Am J Vet Res. November 1991;52(11):1826-30.

 

 

Posted in Acupuncture | 7 Comments

Red Flags of Quackery

Another gem from Sci-ence.org

Posted in Humor | Leave a comment