The SkeptVet

The “Natural” Nonsense that is Applied Zoopharmacognosy

Posted on October 24, 2016 by skeptvet

Introduction
A few years ago, I wrote about an interesting phenomenon called zoopharmacognosy. The idea is that animals might select specific plants or other substances to eat that would have therapeutic effects. An example might be an herbivore with a heavy parasite load eating a plant it doesn’t normally use as food but which happens to reduce the number of those parasites. It’s a popular idea among proponents of herbal medicine and folks who think the word “natural” is a meaningful guide to effective medical treatment because it reinforces their existing beliefs. However, the reality is a lot more complicated than such people seem able to admit.

There is some evidence that animals in the wild sometimes select plants to eat that might have health benefits. The best evidence comes from insects and other species with short generation times that produce large numbers of young and have rather simple, predominantly genetically determined behavior. Evolution can quickly select for changes in behavior that have a selective advantage in such species because small changes can readily spread if they give even a little advantage to a few individuals, and behavior is not very flexible or complex and so can be altered by small genetic changes.

There is much less reason to think zoopharmacognosy is a common or effective behavior found in more complex species, such as mammals. Most of the claims for this are simply uncontrolled observations with lots of assumptions and bias built in. And proponents of this idea generally ignore the fact that the availability of potentially medicinal plants is unpredictable, their composition and effects vary from plant to plant, region to region, and year to year, that we don’t have actual evidence for the real value of most plants considered “medicinal” by various folk medicine traditions, and finally that wild animals poison themselves or ingest non-food objects with deleterious consequences, which argues against a strong and reliable intuition about what is healthful.

Nevertheless, it should come as no surprise that not only do some alternative medicine proponents claim that zoopharmacognosy is an established and widespread phenomenon, rather than an interesting and largely unproven idea, they also use it to validate other ideas that are just as unproven and often even less plausible. Sadly, some even manage to profit from selling the idea, and a host of bogus remedies based on it, to pet owners. One such person is Caroline Ingraham, the proprietor of the grandly named Ingraham Academy of Applied Zoopharmacognosy.

Applied Zoopharmacognosy?
Somehow, Ms. Ingraham has created an apparently successful business selling the idea that your pet somehow knows which “natural medicine” they need for any illness and that she can teach you how to figure out which remedy your pet wants you to give him or her. According to her mission statement:

The Ingraham Academy of Zoopharmacognosy, headed by the founder of Applied Zoopharmacognosy Caroline Ingraham, promotes self-medication as a necessary component of domestic animal health and trains individuals in how to enable and recognize self-medicative behaviour in animals.

Since it is not at all clear that zoopharmacognosy is a real or significant phenomenon among wild or domestic animals, claiming to teach people how to take advantage of it as a “necessary” part of their animals’ care is quite a stretch.

Who is Caroline Ingraham?
Ms. Ingraham does not provide a great deal of information about her background on her web site. While I think her claims should stand (or more likely fall) on the basis of the evidence rather than her credentials, I think it fair to ask whether she has any formal scientific training experience that might explain how she came to develop this questionable approach to veterinary medicine. Unfortunately, all that is available on her web site is this:

Caroline Ingraham founded Applied Zoopharmacognosy and is the leading expert in this field of animal self-medication…. Caroline has featured in many scientific journals and articles, and has written numerous books on the subject.

At 22 years of age, Caroline studied the clinical use of essential oils for humans with one of the world’s leading experts in aromatherapy, Robert Tisserand and during her studies began to develop her approach towards helping animals using essential oils and other plant and mineral remedies. She later went on to study the French approach to the scientific use of essential oils with EORC (France) and Biologist Thomas Ingraham.

Her work encompasses an understanding of pharmacokinetics and pharmacology combined with animal self-medication.

Given that “aromatherapy” is a dubious practice and there is little evidence for any benefits that are not psychological in nature, studying with “experts” in this field is not a credential that carries much weight. And while she has written a number of books about aromatherapy and her invented field of “applied zoopharmacognosy,” I have not yet found any reputable scientific publications from her on these subjects, despite the claim of being “featured in many scientific journals.”

“Medicinal” Plants?
In addition to classes and books Ms. Ingraham happens to sell the remedies she suggests you let you pet choose among. These include essential oils and a range of plant-based products in various forms. Which raises the first of many problems with Ms. Ingraham’s claims: What are the “medicines” are we supposed to offer our pets?

There is no evidence for any meaningful medicinal value to the vast majority of the products that she sells. There is weak evidence for beneficial effects on subjective mood states, such as anxiety, in humans, but the notion that they can influence the outcome of serious diseases is entirely unproven and highly implausible. (1, 2, 3, 4).

And as I have discussed extensively before, herbal medicine is a complex subject, but the bottom line is there is no herbal product proven to have meaningful benefits for serious disease in companion animals. Most herbal products are untested and unreliable in terms of constituents. And there are serious risks to using untested and unregulated plant-based medicines. So whether or not your pet knows what they need to get better and can tell you, how is it helpful to offer them a selection of remedies that haven’t been shown to actually work?

Of course, the underlying reason for this is far more pragmatic. Not being a veterinarian, Ms. Ingraham cannot employ most medicines that have actually been proven to work. And even the “Founder of Applied Zoopharmacognosy” would likely admit that offering a selection of antibiotics, cancer drugs, pain relievers, and so on and letting your pet decide which drug it needed and how much to take would likely not result in a desirable outcome. That would demonstrate real trust in their inherent wisdom!

Undoubtedly, she would claim that this is different from what she recommends because pharmaceutical medicines are “chemicals” and are not “natural” so the inherent wisdom of animals to self-heal doesn’t operate with such remedies. That’s not a convincing argument, especially given that we at least we know the risks and benefits of real medicines, and feeding our pets her essential oils and ground-up leaves is just playing roulette with untested chemicals.

How Our Pets Communicate their Choices
The method by which Ms. Ingraham suggests our pets can indicate their choice of “remedy” is another problem with her approach. Even if our pets have a preference that is meaningful and appropriate (which has not been demonstrated), it is naïve to imagine that we can read our pets body language with a level of specificity that we can tell which remedy that want without introducing our own bias or influencing their behavior. Studies of drug detection dogs have shown that dogs are very sensitive to human expectations and will often misidentify substances they are supposed to search for when their handler has a pre-existing and incorrect belief about where drugs are located. And the caregiver placebo effect is a well-known phenomenon in which owners and veterinarians see what they hope or expect to see in their dogs rather that accurately observing their behavior.

So what cues does Ms. Ingraham suggest we look for in reading our dogs’ choices? Without buying her book or taking her class (and yes, I know her defenders will say I should do so before evaluating the method, so here is where you can find my prior explanations for why this is not a useful or legitimate argument), I was able to find some of her recommended cues on the site where she sells her products:

Positive reactions:

Sniffing

Smelling

Stillness

A vacant look

Blinking

Stretching

Closing the eyes

Lowering the head or lying down

The work is all about not rushing, and closely observing your dog.

Positive reactions mistaken for negative reactions:

Grimacing (helps open the vomeronasal organ)

Barking or lunging at the extract Anxious (behaviour usually signifies a release, followed by calm)

Jumping away quickly, or backing away from the aroma (usually indicates releasing an unpleasant memory)

Negative reaction:

Lack of interest, or distracted

This list has all the specificity of a horoscope or a homeopathic proving. A lack of interest is a negative sign, but a vacant look is a positive sign. Lunging at the remedy indicates selection, but so does backing away from the remedy. Even blinking is supposed to be a positive sign! Clearly, this is a perfect example of the use of vagueness to allow any interpretation the person making the claim desires to be supported. It is exactly the sort of self-deluding approach to animal behavior that lets pet psychics and their clients convince themselves that bit of magical nonsense is real.

What About Eating Socks?
Of course, any claim that our pets know what’s good for them and choose to eat the healthiest food or most appropriate medicinal plants has to consider the inevitable question of why, if they are so wise, do our animal companions try to kill themselves by eating socks, batteries, massive overdoses of medication, their own feces and vomit, and any number of other distinctly unhealthful substances?

Ms. Ingraham’s response to this question also strikes me as pretty unconvincing. Basically, she claims that our animals may be too hungry to resist toxic plants, that they are fooled by “artificial” chemicals or other substances, such as sugar and flavorings, into thinking unhealthy substances are good for them, or that in nature they would eat a natural “antidote” to a toxic plant after eating that pant but that they don’t always have access to such anecdotes in captivity. None of this reasoning makes much sense, and it ignores both the self-destructive ingestive behavior seen in wild animals as well as the impact of domestication on the physiology, diet, and behavior of many animals, such as dogs and livestock.

What’s the Harm?
There are a number of ways in which the idea of “applied zoopharmacognosy” can be harmful to our pets. For one, the remedies Ms. Ingraham recommends are largely untested, and this means not only that they might not be helpful but that we can’t assume they are safe. As I’ve pointed out many times, plant-based chemicals can do plenty of direct harm.

Perhaps the greater risk is the indirect harm caused by relying on nonsense instead of seeking legitimate medical treatment. This is exacerbated by suggesting that this method at be more reliable than conventional medicine, as the ever-unreliable alternative medicine advocate Dr. Karen Becker has done.

To suggest doctors often choose the wrong remedy whereas pets intuitively do a better job when selecting from untested and unregulated alternative products is irresponsible and misleading. And Dr. Becker seems to be forgetting that “wild animals” live shorter lives far richer in parasitism, disease, and suffering than our pets, despite their freedom from misguided doctors and access to “Nature’s pharmacy.”

The following testimonial is a particularly chilling example of how dangerous this sort of delusion can be. A student of Ms. Ingraham describes her use of the nonsense she was taught to treat what she had good reason to believe was a potentially life-threatening illness.

The fact that the owner got away with this response to what might have been a deadly illness does not justify it. The fact that Ms. Ingraham has chosen to post this testimonial on her Facebook page as part of the process of advertising her services suggests she may recommend or approve of using her method and her products in place of proper veterinary care, even in potentially life-threatening situations. That is certainly the impression her student acquired in her class. If this is true, it is a dangerous and irresponsible practice.

Bottom Line
There is little evidence that selection of medicinal plants or other substances by animals in their natural habitat or by domesticated animals is a common behavior with substantial health benefits. Zoopharmacognosy is an interesting phenomenon, but there is very limited evidence for it in most species. Wild animals are generally less healthy and shorter-lived than domesticated animals provided conventional healthcare, nutrition, sanitation, and other basic husbandry, so the concept Ms. Ingraham is selling is mostly a variety of the appeal to nature fallacy.

There is also virtually no evidence that the use of essential oils or many of the plant extracts Ms. Ingraham sells is safe or effective for any serious health condition. Aromatherapy has not been shown even in humans to have significant health benefits, though there may be some mild psychological effects, and in veterinary species there is no reason to think essential oils can dramatically improve health. Likewise, while herbal medicine is a bit more plausible and promising in some ways, it has largely failed to prove its worth in controlled scientific research, and most of the herbal and other plant remedies Ms. Ingraham sells and recommends have not been proven to have value or even to be reliably safe.

The process of letting our pets “select” a remedy is subjective and deeply vulnerable to bias and caregiver placebo effects.

Most importantly, Applied Zoopharmacognosy is yet another unproven and implausible practice that places pets in danger when it is used as a substitute for real veterinary care. Even if the remedies themselves are harmless, which is not certain, the example above illustrates how it can be very dangerous if people are led to believe that these methods and products can replace appropriate medical care.

Posted in General | 1 Comment

Evidence Update- Stem Cell Therapies for Companion Animals

Posted on October 23, 2016 by skeptvet

Introduction
One of the most frequent recurring topics on this blog has been stem cell therapies. Generally, I have concluded that various types of stem cell therapies are plausible and promising, but they are unfortunately being marketed with claims and uses that go far beyond any reasonable scientific evidence. Since the last time I reviewed the subject, a couple of interesting articles have been published, so I thought it was time for an update.

Research Review
The first is a narrative review of companion animal stem cell studies published earlier this year.

Andrew M. Hoffman, Steven W. Dow. Concise Review: Stem Cell Trials Using Companion Animal Disease Models .STEM CELLS 2016;34:1709–1729

As a narrative review, this paper does not have the rigor, controls for bias, or focus of a systematic review. However, it provides a nice informal summary of the problems for which stem cell therapies have been investigated in companion animals, the different types of therapies evaluated, and the strengths and weakness of the literature. The paper reviewed companion animal stem cell studies from 2008 through 2015.

The key findings are that there are not many studies, the studies that exist are very inconsistent in terms of the specific treatment they tested, and almost all of the studies have significant limitations.

Arthritis is the most common problem for which stem cell therapies have been investigate in companion animals. However, the specific therapies used are always somewhat different, so there is no replication or consistency in the literature. Studies use different doses, preparation methods, methods of administration, sources of stem cells, and measures of effect. This hodgepodge of methods indicates the very early stage of research in this area, and we cannot yet draw reliable conclusions about the value or safety of particular products for specific uses. And most studies included only a handful of patients, which significantly weakens any conclusions based on them.

In addition, the majority of the studies did not employ the basic mechanisms of controlling for bias and error, including randomization of subjects, blinding of clients and investigators, and placebo controls. Subjective measures of effect were also most commonly used, which make the lack of such bias control methods particularly significant. While most studies claimed to find some beneficial effects, these claims have to be taken with a grain of salt due to these methodological issues.

The same general issues pertained to the other clinical problems for which stem cells have been studied. Intervertebral disk disease, inflammatory bowel disease, dry eye, kidney disease, and a few other conditions have been the subject of stem cell studies. These again involved very few patients, a variety of quite different treatments, and few if any controls for bias, confounding, and other important kinds of error. The results were inconsistent, some showing apparent benefits and others not, and a few showed evidence of some short-term side-effects. Overall, no general conclusion about the clinical value of stem cell therapies for any of these conditions can be justified by the existing research.

The authors conducted the review primary to make the case that companion animals might make a good research field for studying stem cell therapies with a long-term goal of applying them to humans. However, even with an optimistic slant, the authors’ conclusions were quite cautious:

In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies.

However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models… Based on review of the literature, the utility of companion animals in stem cell trials is in the very early stages.

They also provided some recommendations for ways to improve the companion animal literature on stem cells, which would benefit both those with the ultimate goal of treating humans and those of us interested in finding safe and effective treatments for veterinary patients.

To facilitate expanded development and application of companion animal disease model research in the future, the following areas need to be addressed with additional education, communication, and industry and government support:

Increased collaborations between physicians and veterinarians to address specific disease conditions and models, consistent with the One Health paradigm.

Increased understanding of the molecular pathology of specific diseases in companion animals, and detailed comparison to human samples and analogous disease processes.

Greater characterization of companion animal stem cells and their cellular products.

The use of more rigorous double blind (owner, investigator) randomized clinical trial designs whenever possible. Education of the public about the value placebo-controlled studies.

Greater clinical trial infrastructure (personnel, equipment, specialized instrumentation, and imaging) to support efficient recruitment into clinical trials.

Central registry of veterinary clinical trials (currently in progress at the American Veterinary Medical Association).

Biorepositories and registries of companion animal disease tissue, biofluids, and nucleic acids or other samples.

Improved availability of companion animal specific reagents, in particular probes for protein detection and quantification.

The application of FDA guidance (NADA, INAD, pre-IND) in clinical trials involving stem cell treatments in companion animals (client owned animals).

I have highlighted a few of the recommendations of particular importance for making such research useful to veterinary patients. The establishment of a clinical trial registry, improved rigor and quality of research, and the application of FDA-level standards would all greatly improve the quality of stem cell research in veterinary medicine and improve the chances of finding truly useful therapies. This last measure is particularly relevant to the other study I wanted to discuss.

Allogenic Stem Cells for Arthritis

Harman R, Carlson K, Gaynor J, et al. A Prospective, Randomized, Masked, and Placebo-Controlled Efficacy Study of Intraarticular Allogeneic Adipose Stem Cells for the Treatment of Osteoarthritis in Dogs. Frontiers in Veterinary Science. 2016;3:81.

This is by far the best quality stem cell research study I have yet seen, and the reason is likely that the study is part of an effort to get FDA approval for a specific stem cell treatment. While the study has limitations, as all research does, it is well-designed and conducted and provides pretty robust results.

The major limitations are that the study was industry funded, which has been associated with some risk of bias in human pharmaceutical research, and the outcome measures were quite subjective. However, the mechanisms for controlling potential bias were quite thorough, including appropriate randomization, blinding, pre-specific outcome measures, and a lack of the statistical hocus pocus that is so common in veterinary clinical trials. Overall, the study provides very good evidence for a potentially clinically meaningful effect.

Interestingly, the study investigated a allogenic stem cell product, meaning one derived for a dog other than the intended patient. Most current stem cell products used in companion animals involve taking fat or blood form a patient, processing it in various ways, and then using that product in the same patient (called autologous stem cell therapy). While this has some advantages in terms of minimizing the risk of infections and adverse reactions to foreign material, it requires these patients to undergo anesthesia and surgery to collect the sample, which has its own risks and costs, and it yields inconsistent material for treatment. An off-the-shelf stem cell product derived from a single patient and then processed and maintained by the manufacturer can be better standardized and assessed for quality, it can be a more predictable therapy, and it can avoid additional anesthetic and surgical procedures for patients, so there are some advantages to this approach.

The study randomized 93 dogs with arthritis in one or more joints to treatment with the stem cell product or a placebo injected into the affected joints. 74 of the subjects were included in the final analysis, with the rest being excluded for failing to adhere to the study procedures or other reasons. The primary outcome was the owner assessment 60 days after treatment of three specific activities chosen by the owner at the beginning as important measures of comfort and function. The secondary outcomes were assessments by the veterinarians treating the patient and overall assessments by both owner and vet. These are inherently subjective outcome measures, which are somewhat less reliable than more objective measures, such as force-plate analysis. However, the mechanisms for minimizing bias were good enough to make these reasonable choices despite the potential for caregiver placebo effects.

The primary outcome showed both a statistically significant and a clinically meaningful difference of about 24% in degree of improvement between placebo and treatment groups. In other words, the placebo group owners reported a 55% improvement, which shows how strong a placebo effect by proxy can occur. However, the treatment group owners showed a 79% improvement, which is enough of a difference to suggest some real change.

The veterinarian assessments also showed large and significantly greater improvements in the treatment group compared to the placebo group. The overall owner assessment was the only measure to show a difference too small to be statistically significant. However, the size of the effect and the consistency of the effect across different measures are arguably more important.

So overall, the study strongly suggests this particular stem cell treatment had some real beneficial effects, and no significant undesirable effects were noted, though with stem cells many of the problems they might cause would not necessarily be expected to appear only 60 days after treatment. This does not, of course, validate all of the myriad of stem cell therapies and uses of these out there. In particular, it doesn’t necessarily tell us that the autologous stem cell products which are most widely used have similar benefits.

Naturally, no single study is ever sufficient alone to prove safety and efficacy. The FDA approval will likely involve further research which hopefully will support these findings. If so, this would be an important step towards producing a reliable and consistently effective stem cell treatment for arthritis in dogs. I have always been cautiously hopeful about this approach, and I am pleased to see the very beginnings of the kind of research evidence needed to make stem cell treatments a reasonably evidence-based procedure.

Bottom Line
Overall, the evidence supporting stem cell therapies in companion animals is very weak and preliminary. More research is absolutely appropriate, but clinical use is still an uncontrolled experiment on our patients and should only be done with clear and detailed discussion with owners about the uncertain risks and benefits and after all treatments with better supporting evidence have been considered.

The best evidence so far, a clinical trial involving treatment of dogs with arthritis, does suggest that allogenic stem cells injected into arthritic joints may improve comfort and function enough to be worthwhile, with no apparent short-term side-effects. Even for this process, however, more research is needed to justify widespread use. Hopefully, this will emerge in the course of pursuing FDA approval for this method.

Posted in Science-Based Veterinary Medicine | 2 Comments

Overdiagnosis

Posted on October 10, 2016 by skeptvet

Overdiagnosis is now recognized as a common and serious problem in human medicine that causes substantial harm in terms of unnecessary costs, wasted resources, and patient and caregiving suffering. International conferences (e.g. Preventing Overdiagnosis) and special features in major medical journals (e.g. Too Much Medicine in the British Medical Journal and Less is More in the AMA journal) have been dedicated to discussions of overdiagnosis and overtreatment. In 2012, a consortium of 70 specialty groups created the online resource Choosing Wisely to help physicians and patients make evidence-based decisions that reduce overdiagnosis and overtreatment. Even an influential popular book has been written on the subject: Overdiagnosed: Making people sick in the pursuit of health.

Changes in clinical practice guidelines and public education strategies have resulted from the growing recognition of the risk of overdiagnosis in human medicine, including highly publicized changes in recommendations for prostate cancer screening in men and breast cancer screening in women.

However, there seems to be little discussion in the veterinary literature or veterinary curriculum of the problem of overdiagnosis and the risks it poses to veterinary patients. In the past, IK have discussed the evidence regarding potential sources of overdiagnosis in veterinary medicine, such as pre-anesthetic blood testing (also c.f. 1, 2). However, among veterinarians and animal owners, there seems to be a near total lack of awareness of the fact that sometimes testing for and diagnosing a condition can actually lead to a worse outcome for the patient than not diagnosing it.

This is a counterintuitive idea, but it is well-established in human medicine. Changes in guidelines for prostate cancer screening, breast cancer screening, thyroid cancer testing, and many other conditions have come about because of the recognition that inappropriately targeted diagnostic tests can harm patients and waste resources on treatments that do not make people better. It is time we took a serious look at this issue in veterinary medicine, and made an effort to collect the data needed to understand its scope and causes so that we can better serve our patients. Since I was unable to find virtually any discussion of the subject in the veterinary literature, I have written a commentary raising the subject, which I hope will stimulate needed discussions on this topic.

McKenzie, BA. Overdiagnosis. Journal of the American Veterinary Medical Association. 2016:249(8);884-889.

Posted in General, Science-Based Veterinary Medicine | 2 Comments

Evidence Update- Yunnan Baiyao: Still No Persuasive Evidence of any Benefits

Posted on October 3, 2016 by skeptvet

Back in 2010, in the early days of this blog, I reviewed the evidence for the Chinese herbal supplement Yunnan Baiyao. At the time, I found only very low-quality evidence concerning the potential risks and benefits of this product. Some in vitro studies suggested possible mechanisms by which the product might help limit bleeding. However, clinical trials were sparse, low quality, and often at high risk of bias. Many studies have been conducted in China, and these must be viewed very skeptically given that past reviews have found extreme publication bias for alternative medicine studies in China (one review found absolutely no negative studies were published there), and a recent investigation by the Chinese government found up to 80% of drug trials published there were fraudulent or otherwise unreliable. Also deeply concerning was the fact that the company producing the product refuses to disclose its exact ingredients.

So the bottom line in 2010 was that Yunnan Baiyao is an unregulated and largely untested secret recipe, and it is unclear how it can have its purported effect, stopping bleeding, without having any potential risks, including most obviously excessive blot clotting, which is the cause of strokes and other serious medical problems. So what new information is there since 2010?

There have been a few additional studies published, but they tend to fit the profile of those already available five years ago: mostly from China and mostly not clinical trials with robust design and execution. A couple of new studies have been published directly related to veterinary use.

Shmalberg J, Hill RC, Scott KC. Nutrient and metal analyses of Chinese herbal products marketed for veterinary use. J Anim Physiol Anim Nutr (Berl). 2013 Apr;97(2):305-14

This study evaluated the nutrient and metal content of a number of Chinese herbal products, including Yunnan Baiyao. The Yunnan Baiyao did contain potentially toxic heavy metals, such as lead, though the single batch tested suggested the levels were probably not high enough to cause illness, at least at typical doses over a limited period of time.

Wirth KA, Kow K, Salute ME, Bacon NJ, Milner RJ. In vitro effects of Yunnan Baiyao on canine hemangiosarcoma cell lines. Vet Comp Oncol. 2016 Sep;14(3):281-94.

This study found that Yunnan Baiyao could kill cells of the canine cancer hemangiosarcoma in vitro. This kind of study is a necessary precursor to clinical testing of drugs, but it is important to point out that it says nothing about whether the substance tested would be useful in actual patients. Bleach, for example, kills cancer cells in vitro, but that doesn’t make it a useful cancer drug.

Murphy LA, Panek CM, Bianco D, Nakamura RK. Use of Yunnan Baiyao and epsilon aminocaproic acid in dogs with right atrial masses and pericardial effusion. J Vet Emerg Crit Care (San Antonio). 2016 Sep 26. doi: 10.1111/vec.12529. [Epub ahead of print]

This study actually evaluated a common clinical use for Yunnan Baiyao. Dogs with tumors on the right atrium of the heart and fluid in the pericardium, the sac around the heart, almost always have a type of cancer known as hemangiosarcoma. This cancer typically lodges in places like the spleen, liver, or heart, and it usually causes severe bleeding. The conventional therapies available aren’t very effective, and most dogs with this disease die or are euthanized within a few days to a few months. As always, there are exceptions who survive much longer, but generally the outlook for this disease is poor, especially for the form that occurs in the heart.

The lack of highly effective conventional treatment makes this disease a popular target for alternative therapies, and Yunnan Baiyao has come to be used fairly frequently. Though the evidence has not been available to substantiate any benefits, there is a “what is there to lose?” attitude in these cases, so even many conventional vets are willing to give it a try. Though there are, as always, plenty of miraculous anecdotes out there (and, of course, not many negative ones since who goes out of their way to tell everyone about something they tried that didn’t work?), this study is the first formal research in regular clinical patients.

The study was retrospective, meaning that the authors simply looked through records of animals that had been treated for a right atrial mass and fluid around the heart. Some were treated with only conventional supportive care, and some got Yunnan Baiyao, either alone or with another potential anti-bleeding drug called aminocaproic acid. There was no randomization and no blinding, so it is possible that any results could be due to factors other than the drugs given. However, the authors checked for differences in many characteristics of the patients that might influence the results and didn’t find any.

So what were the results?

The median time to recurrence of clinical signs in the treated group (12 d, range 1–186 d) was not significantly different from the control group (14.5 d, range 1–277 d)…The median survival time of dogs in the treated group (18d, range 1–186 d) was not significantly improved compared to the control group (16 d, range 1–277 d; Table 1, Figure 1). The median survival of the 8 dogs that received YB and EAC (17 d, range 1–88 d) was also not significantly improved compared to the 16 dogs that received YB alone (31 d, range 1–186 d). There were no side effects attributed to the YB or EAC use in any dogs during the study period.

Basically, there were no differences in any of the symptoms or in the survival of dogs whether or not they got Yunnan Baiyao. There were no apparent side effects either, but that isn’t too surprising in a group of dogs that only lives 2-4 weeks after being treated.

While this study, like all research has limitations, it is the best evidence concerning real-world clinical use of Yunnan Baiyao in dogs so far, and it found no effect at all. This is not the final word on the subject, of course, since there are other conditions, other circumstances, other doses, and all sorts of other ways in which the product could be tested. However, as of now the evidence does not support any benefits. And the fact that, as the authors point out, “its

exact compositional formula is a closely guarded secret by the manufactures and like many nutritional supplements, is not subjected to any quality control measures as compared to pharmaceuticals.” Most vets, and certainly most alternative medicine vets, would lose their minds if it was suggested we should use a drug company product not only without evidence of effectiveness but without even knowing what is in it! Yet, for some reason, a different standard is often applied to herbal remedies like Yunnan Baiyao, which places our patients at unnecessary risk.

Bottom Line

Despite some suggestive in vitro and low-quality studies, the best evidence available so far does not support that Yunnan Baiyao has any benefit for dogs. The fact that it is unregulated, that there is demonstrated inconsistency in the mineral and metal contents of Yunnan Baiyao from different sources, and that the ingredients are still kept secret by the manufacturers, should also give clinicians pause in considering this for their patients. While use in desperate circumstances when there are no established effective therapies may be reasonable, clients should clearly understand that this is at best a rolling of the dice and that the safety and effectiveness of this product for any use has not been established.

Posted in Herbs and Supplements | Leave a comment

IAABC Interview Discussing CAVM and EBVM

Posted on October 3, 2016 by skeptvet

Here is an interview I did recently with an association of animal behavior consultants. We discussed a number of subjects that appear frequently here, including the role of evidence and anecdote in evaluating treatments for animals, and the risks of alternative medicine.

Posted in Presentations, Lectures, Publications & Interviews | 1 Comment

Scientists Warn that Donald Trump is the Most Anti-Science Candidate for President

Posted on September 29, 2016 by skeptvet

Since my review of the presidential candidates’ positions on science issues earlier in the week, I have seen a number of efforts by other scientists to warn the scientific community and the public that Donald Trump stands out as the most egregiously and consistently anti-science candidate in this year’s election.

One effort is an open letter authored by a number of prominent scientists, including Harriett Hall and Steven Novella, two prominent skeptics and authors of the Science-Based Medicine Blog:

Scientists say: “Donald Trump is Not Who We Are”

As members of the scientific community, we invite our colleagues to stand together in making it clear that Donald Trump’s views on many pressing topics are at odds with scientific reality and represent a dangerous rejection of scientific thinking.

There should be no place for this kind of rhetoric – or this kind of attitude toward expertise itself – in the halls of government.

As a community, we affirm the values that make us who we are: curiosity, skepticism, integrity, and simple adherence to the facts.

Vaccines save lives every day, but Mr. Trump has stoked discredited fears about vaccines and autism and accused doctors of lying to people about them.

Every major country on Earth is adapting to a changing climate and reducing emissions from fossil fuels, but Mr. Trump has claimed it is a hoax, a statement that prompted a response from hundreds of members of the U.S. National Academy of Sciences, the country’s leading scientific advisory body.

Mr. Trump’s running mate, Mike Pence, has a similarly disconcerting record:

He also dismisses the evidence that climate change is caused by burning fossil fuels.

He delivered a speech to the House of Representatives challenging the teaching of evolutionary science in classrooms based on a misreading of how evolution works.

Nearly 40 years after the Surgeon General first warned us about the dangers of smoking, Pence claimed that “smoking doesn’t kill” and said there was no direct link between smoking and lung disease.

These are not the words and thoughts of responsible leaders.

The letter currently has 712 signatures, including mine.

Another open letter signed by 375 members of the National Academy of Sciences warns of the dangers of denial of human-caused climate change and of a refusal to participate in international efforts to combat it, both positions embraced by Donald Trump and rejected by all of the other candidates:

An Open Letter Regarding Climate Change From Concerned Members of the U.S. National Academy of Sciences

Human-caused climate change is not a belief, a hoax, or a conspiracy. It is a physical reality.

During the Presidential primary campaign, claims were made that the Earth is not warming, or that warming is due to purely natural causes outside of human control. Such claims are inconsistent with reality.

The political system also has tipping points. Thus it is of great concern that the Republican nominee for President has advocated U.S. withdrawal from the Paris Accord. A “Parexit” would send a clear signal to the rest of the world: “The United States does not care about the global problem of human-caused climate change. You are on your own.” Such a decision would make it far more difficult to develop effective global strategies for mitigating and adapting to climate change.

Posted in Law, Regulation, and Politics | Leave a comment

Science and Presidential Politics

Posted on September 27, 2016 by skeptvet

I generally try to stay away from politics per se on this blog, though I often cover political issues when they touch on the areas of science and alternative medicine. Usually, this falls in the general category of government failure to regulate unproven or pseudoscientific therapies properly or protect the public from quackery. However, this post is more directly about the current election. Regardless of your political perspective or which candidate you support on the basis of other issues, there is a bit of information out there concerning the presidential candidates’ positions on science issues, and that is what I’m going to address today.

Since 2008, the non-profit, non-partisan group ScienceDebate has been trying to get all major and third-party candidates for president to participate in a debate specifically focused on science and technology issues. Such a debate, sadly, has never happened, which says a lot about the degree to which science is valued by politicians and voters. However, candidates often provide written answers to questions about science policy, which allows some comparison of their knowledge and views on these topics.

Both Trump and Clinton, as well as Green Party candidate Jill Stein and Libertarian Gary Johnson, provided answers to these questions this year. There isn’t much surprising about these answers.

Clinton

Clinton’s answers reflect a mainstream moderate-left view, and in general she makes moderately specific policy proposals involving increasing government investment and/or regulation. Her responses are the longest and most specific and substantive of the candidates. In particular, she acknowledges anthropogenic climate change and supports international efforts to combat it, and she is a strong proponent of vaccination and public health programs.

Apart from her answers on this questionnaire, Clinton has been frustratingly sympathetic to naturopathy and some varieties of alternative medicine, so she is by no means a crusader for a strongly science-based approach to medicine. And her positions on GMOs have been inconsistent.

Stein

The positions of the minor party candidates also fit pretty closely the expectations one would have based on their political affiliations. Jill Stein’s answers mostly emphasize environmental protection positions, such as aggressive action on climate change. Unfortunately, she also strongly supports a number of positions suggesting she is either misinformed about the scientific evidence or prefers ideology to scientific facts. She aggressively promotes organic agricultures, despite the lack of evidence to support any health benefits. This may be because of perceived environmental benefits, and there is somewhat better evidence for these, though is also controversy on this subject. Stein is also strongly opposed to GMO research and supports misleading labeling laws intended to discourage progress in this area, which reflects a fear of GMO not supported by the evidence.

While Stein has been accused of being anti-vaccine, the evidence does not support that view. She does tend to respond to any question about vaccines by talking mostly about conflict-of-interest issues within regulatory agencies and suggesting that distrust of vaccination is driven more by this than anti-vaccine propaganda. I tend to agree with concerns about conflict-of-interest, but I disagree that this is the major driver of anti-vaccine fears. I think complaints about industry and government relations, even when often valid, are used as a justification for anti-vaccine ideologies based more in pseudoscience and fear than in genuine concern about impartial science. However, her statements suggest that despite this rhetorical focus, she appears to accept the scientific consensus on the safety and benefits of vaccination, she’s just less concerned about those issues than about big bad corporations.

It’s also true that the Green Party platform has been supportive of homeopathy and other alternative therapies. That has been dropped from the current platform, though it was present when Stein was the nominee in 2012. Finally, Stein is also adamantly opposed to any use of nuclear power under any circumstances, without any apparent interest in the scientific evidence concerning the pros and cons of it.

Johnson

Libertarian Gary Johnson, not surprisingly, answers pretty much all of the questions in a way that allows him to emphasize his view that government is almost always the problem and not the solution. He rarely has much to say about the scientific issues per se, since he’s much more concerned about free markets and eliminating most government functions. Though he doesn’t say much about science, his answers generally don’t reveal any significant departures from mainstream science. He even appears, grudgingly and weakly, to accept a role of human activity in climate change and the need for compulsory vaccination, at least sometimes.

Johnson is, however, adamantly opposed to any meaningful regulatory role for the FDA in drug safety, which is clearly counter to the best interests of patients. And I suspect he would support the continued lack of meaningful regulation of dietary supplements, herbal remedies, and so on, in favor of the “buyer beware” approach, which proved utterly ineffective in the 18^th and 19^th centuries.

Donald Trump

And then there’s Donald Trump. Without question, his ScienceDebate answers and other comments make him soundly the most anti-science candidate running, in terms of positive policy positions and a general ignorance of the issues and the facts. His answers to the questions are typically short, vague, and often completely off point, indicating a total lack of interest in the subject. Overall, he too disdains much role for government in science and technology, preferring the free market to be allowed to do as it pleases. His response to the issue of public health strongly suggests he sees little to no value in the national public health system or institutions.

Where Trump sets himself apart from the other candidates in terms of science issues is in his rejection of climate change science and his deeply anti-vaccination views. He has indicated a belief that climate change is not real and is merely a ploy to give China an economic advantage over the U.S. And he is the candidate of choice for the anti-vaccine movement due to his open acceptance of the tired and long-disproven myth that vaccines cause autism. Here are some examples of how popular Trump is with the anti-vaccine crowd.

The keynote conclusion of this article on the notorious quackery site is this:

This November, VOTE TRUMP or prepare for the DEATH of everything you love

Subtle, eh? Here’s another example:

Yup, that’s right. The uber anti-vaxer Andrew Wakefield has been personally assured by Trump that he understands vaccines cause autism. This endorsement has brought along other anti-vaccine loons, including veterinarians like the notorious Patricia Jordan, author of the bizarre extremist screed Vaccinosis-The Mark of the Beast, about whom I’ve written frequently. And another inhabitant of an alternate reality I’ve written about, Dr. Al Plechner (Here and Here), also appears to be a Trump supporter, though for somewhat different reasons. Here are a few snippets from his Facebook page:

Trump has also been quite friendly towards alternative medicine. He has had business interests involving quack urine testing and vitamin and diet schemes. However, this may be more a reflection of his greed and lack of business ethics than a sign of a true ideological commitment to alternative medicine.

Bottom Line
None of the candidates have a spotless record in terms of science policy positions. Politics, values, personal experience, and emotions often trump scientific evidence in the development and defense of beliefs. However, Donald Trump has consistently inhabited an alternate reality and shown flagrant disregard for facts and experts in many areas, and science is no exception. His embrace of anti-vaccine myths, and the support this has generated from the anti-vaxer fringe, as well as his denial of climate change science make him easily the most egregiously and consistently anti-science candidate in the field.

Posted in Law, Regulation, and Politics | 1 Comment

More Evidence that Laboratory Testing of Healthy Dogs and Cats Uncovers Lots of Abnormalities of Questionable Significance

Posted on September 25, 2016 by skeptvet

A new article has just been published adding some information to a subject I’ve addressed before, the value of blood testing and other diagnostics in clinical health dogs and cats (discussed Here and Here). In the past, I have come to the following conclusions on this subject:

If you test, you will find abnormalities
The clinical significance of these abnormalities is often unclear
You will find more abnormalities, and these will be easier to interpret, if pre-test probability is high, that is if there is a reason to suspect a real medical problem. For example,

Some symptoms of a problem in the history
Some identifiable abnormality in the physical exam

There is, as yet, no evidence that most tests of healthy veterinary patients reduce the occurrence of disease or death

This paper seems to support these conclusions and the results of previous research.

Dell’Osa D, Jaensch S. Prevalence of clinicopathological changes in healthy middle-aged dogs and cats presenting to veterinary practices for routine procedures. Aust Vet J. 2016 Sep;94(9):317-23

The authors did a wide range of blood tests and a urinalysis on 406 dogs 5-8 years old and 130 cats 6-9 years old who came to the vet for routine examination, vaccination, parasite treatment, and other reasons but without an ongoing or new medical problem. This population is probable fairly representative of those animals who come to see their veterinarian when they are healthy, though of course it doesn’t represent well those who only come when ill or who don’t get regular veterinary care.

The study results certainly confirm that when you test healthy individuals, you will find abnormalities and most of those abnormalities will either not represent real disease or will be difficult to interpret.

86% of dogs had one or more abnormality. Only 6.2% of these were subjectively judged to justify further evaluation.
80% of cats had one or more abnormality. Only 19.2% of these were subjectively judged to justify further evaluation.

Common abnormalities that were judged to be errors, testing artefacts, or otherwise clinically unimportant included:

124 cats had abnormal platelet counts, none of which were thought to be real or important
Electrolyte abnormalities and liver enzyme elevations were common in dogs and were generally mild and considered insignificant
Low thyroid hormone levels were frequently seen without any clinical evidence of thyroid disease
High red blood cell concentrations were common and attributed to excitement from the visit and blood sampling
A number of dogs and cats had enzyme elevations that suggested the presence of pancreatitis, though none have clinical symptoms of this problem

The authors did not provide any information on the final diagnosis or clinical outcomes for the animals in this study, so it is impossible, in most cases, to tell how many might have had actual disease or been helped or harmed by the initial and subsequent testing and treatment. They did identify 3 cats (2%) and 5 dogs (1.2%) with Stage 2 or 3 kidney disease. There is evidence that diet change can prolong survival in asymptomatic animals with Stage 2 or higher kidney disease, so a case can be made that these results would likely have benefitted the patients if their owners followed recommended treatment guidelines.

However, there was no other information to identify any benefit or harm from this testing to the animals in the study. This is one of the common problems with research in this area. It is clear that performing diagnostic tests without any specific reason to do so will uncover abnormalities. What is not clear, is how often these results will lead to benefit to the patient through detection and treatment of disease.

As I have discussed previously, there is a real risk of overdiagnosis and overtreatment associated with diagnostic tests done without any specific clinical suspicion of a disease. Most will be meaningless, and this is, at least, a waste of money and resources. Some will be incorrect, as many of the results in this study likely were (especially platelet counts, thyroid testing, and pancreatitis testing). This can lead to unnecessary further tests or treatment, which not only wastes resources but can cause direct harm to patients.

It is also unclear how clients will react to abnormalities, whether or not the veterinarian believes them to be significant. If I tell an owner their older animal has Stage 1 kidney disease, mild liver enzyme elevations, or mild chronic anemia, it is quite possible they will come to view their pet is sick or “aging.” This can easily lead owners to decline testing and treatment that might actually benefit the pet. Comments like, “Well, he has kidney disease,” or “He already has a liver problem” are often made prior to declining dentistry, surgery for curable tumors, and other treatments I recommend for older pets.

Generally, screening tests like these of healthy individuals are very seldom recommended because the evidence has been developed to show they offer few benefits and some real risks. The authors of this paper make the fair observation that this might be different in veterinary medicine since we get less direct information from our patients about how they feel, so we may not be able to pick up signs of disease as soon as in humans. However, the evidence doesn’t exist to demonstrate this hypothesis, as reasonable as it is. And often, the evidence does not exist to show we can do anything useful to help animals with asymptomatic disease in most cases (kidney disease being an exception). So the value of a diagnosis in the face of no available treatment is somewhat questionable.

The subject of overdiagnosis is controversial, and discussions about it often become emotional. It is very difficult not to fall prey to anecdotal reasoning, especially in the absence of high-quality controlled research evidence. However, just as we frequently extrapolate in our testing and treatments from human medicine, it is reasonable to consider the evidence from human medicine that overdiagnosis is a real risk, and there may be times when not testing, especially in individuals who are clinically well, may be the best choice. I’m not arguing that such testing is not beneficial or is harmful, only that we don’t yet have the evidence to say for sure, most of our thinking on this subject is anecdotal, and we rarely consider the possible costs and risks of such testing.

Posted in General, Science-Based Veterinary Medicine | 1 Comment

Update- Hemopet Sues Pet Food Companies to Claim Ownership of the Idea of Nutrigenomics

Posted on September 23, 2016 by skeptvet

Way back in 2012, I wrote about a lawsuit filed by Hemopet, an organization known primarily for being a non-profit blood bank but also involved in some unconventional laboratory testing (as Hemolife) and alternative medicine ( as the Hemopet Holistic Care Center). This founder and director of this organization is Dr. Jean Dodds, about whom I’ve written several times as she is a prominent advocate for a number of alternative medicine practices. Dr. Dodds, via the Hemopet organization, has filed a number of patents for her unconventional diagnostic tests (involving thyroid disease testing and food allergy detection) and for her proposed method to use genetic data to predict the appropriate diet for pets. She originally sued a couple of pet food companies (Purina and Hills) claiming that the very idea of “nutrigenomics,” or using genetic information to formulate diets, was owned by her through these patents.

Though I have since reviewed in detail Dr. Dodds dubious claims about nutrigenomics, her bogus food allergy testing process Nutriscan, and her misleading “studies” on vaccine dosing for small dogs (here and again here), I had lost track of this lawsuit. However, a recent VIN News article about Hemopet drew my attention back to the organization. This article was actually not about the lawsuit but an unrelated issue. Apparently, Hemopet had been pushing the State of California for a tax exemption and implying that its blood-banking service might have to close if the exemption wasn’t granted. The legislation granting the exemption was passed by the legislature but vetoed by the governor. However, Hemopet now says it will remain in operation and will continue to press the state not to require it to pay some $81,000 in back taxes.

This is an interesting subject in its own right. The relationship between the blood bank, diagnostic laboratory, and clinical practice isn’t entirely clear from the Hemopet tax and non-profit filings available on the California DOJ web site. Perhaps something I’ll investigate another time, but as a vet rather than a tax attorney, I’m not sure I can make heads or tails of such issues. In any case, the subject did draw my attention back to the lawsuit I originally wrote about, and this led me to find the subsequent developments I’m reporting here.

In the original post, I concluded that the subject of Hemopet’s nutrigenomics patents seemed to me entirely too vague to qualify for patent protection, though I acknowledged I’m no expert in the subject:

So what appears to have been patented here is the idea of collecting a wide range of pieces of information about an animal in a computer, passing it around to people, and using it to “reduce morbidity and mortality, and improve the quality of life and lifespan” in companion animals. It’s hard to see how this could be a patentable idea, or even truly original apart from the unsubstantiated general claims about the links between gene sequences and health, but again I’m not expert in patent law.

I was more concerned by the lack of a clearly valid and established scientific principle behind the attempt to own the concept of nutrigenomics:

despite a list of scientific papers included with the patent application (but not used as specific citations to support particular claims), it’s not clear that there is an actual preventative or therapeutic healthcare intervention here…it’s a bit baffling how these two organization can compete for ownership of an idea which doesn’t really exist in a tangible form yet…It does seem, however, like putting the cart before the horse, since who gets to profit from a new approach to health and nutrition should at least have something to do with whether the approach actually works and who has done the work to demonstrate this.

Based on my exhaustive review of Dr. Dodds’ subsequent book on nutrigenomics from last year, it’s clear that she still has not validated her concepts or methods, despite now selling them as a product. That, at least, is sufficiently within my area of expertise for me to be able to state with some confidence. However, I was pleased to see that the courts have so far agreed with my far less informed view of the intellectual property questions as well. In November, 2014, the U.S. District Court in California granted a motion by one defendant, Hill’s Pet Nutrition, Inc., for summary dismissal of the lawsuit. The decision explains why, according to legal precedent, the claims made by Hemopet are insufficient to qualify for patent protection, so the patents are not valid nor defensible:

…the formulation and preparation of pet food is nothing more than an extension of the abstract idea of “determine” a dog or cat’s diet. The creating or formulating processes directed in the claims are couched in the most general terms, lacking any specifics that would allow a practitioner to learn how to actually develop or produce such a diet…Therefore, all of the claims are squarely within the realm of “abstract ideas” as defined by the Supreme Court.

Only the final step, “determine a nutritional diet for the canine or feline companion animal; and formulate and prepare a nutritional diet product based on the relationship,” relates to the creation of a “different state or thing.” However, whether considered individually or in combination with the other steps, the claims do nothing more than instruct the practitioner to implement the abstract ideas of the first few unpatentable steps in the final step…This is nothing more than telling the practitioner to “apply it” in general terms. Hemopet’s claims do not describe in detail a step-by-step method for developing a nutritional diet product.

…the functions performed by the computer, database, or software routine at each step of Hemopet’s process are “well-understood, routine, conventional activity, previously engaged in by those in the field.”

[Hemopet’s] claims simply recite the abstract concept of determining a nutritional diet for a dog or cat based on naturally occurring relationships and fail to include any express language to define how the nutritional diet is actually formulated, developed, or produced.

For these reasons, the Court finds that the claims at issue are drawn to a patent-ineligible abstract idea.

The bottom line is that in addition to being scientifically dubious and unproven, Hemopet’s claims about Nutriscan are vague and amount to no more than a rearranging of established and theoretical ideas about genetics and nutrition, not a specific and original process for selecting and formulating a diet. As such, they don’t qualify for patent protection.

This judgement was upheld by the appellate Circuit Court in September, 2015. I have not been able to ascertain what happened with the separate lawsuit on the same grounds filed against Nestle Purina Pet Care, Inc. If anyone with greater legal research skills would like to look into this, I’d be interested in the outcome. However, it appears likely that the outcome of that case was substantially the same as the case against Hill’s, because now Hemopet has filed an appeal in the Hill’s case with the U.S. Supreme Court.

Given that Hemopet’s claims appear vague and unpatentable even to me, and more importantly to the far more qualified judgement of the state district court judge and the federal appeals court judges, it is hard to imagine the Supreme Court granting this appeal. Of course, even if it does that won’t speak at all to the scientific legitimacy of the ideas Hemopet claims to own. But even from a scientific perspective, the ownership of general ideas seems counter to the spirit of scientific discovery and likely to impede research and discovery. I think it far more likely that beneficial therapies and inventions will come from allowing widespread dissemination of ideas and information and from research by many different and competing parties.

Posted in Law, Regulation, and Politics | 3 Comments