About six months ago, I reported on the application of a group of veterinarians belonging to the American College of Veterinary Botanical Medicine (ACVBM) for status as a medical specialty group. I explained the main reasons why, despite the potential value of herbal medicine, such status is not warranted at this time:

1. There is very little high-quality or reliable scientific evidence to support the use of herbal products in veterinary patients.
2. Herbal prescribing is dominated by Chinese Medicine, Ayurveda, and other unscientific folk belief systems, and those proponents who take a more scientific approach are a small minority generally unwilling to reject the claims or methods of alternative herbal medicine.
3. Herbal products are unregulated, inconsistent and unpredictable in their chemical composition, frequently contaminated with toxins or even undisclosed pharmaceutical drugs, and almost none have been properly tested for safety or efficacy. There is ample evidence of serious harm to human patients from herbal products. The ACVBM supports industry self-regulation rather than the kind of government oversight accepted as necessary for pharmaceutical medicines without any sound reason for doing so.
4. The majority of the leadership of the ACVBM are dedicated proponents of alternative medicine, not only for herbal products but homeopathy, acupuncture, energy medicine, and many other unproven or pseudoscientific practices. Many have said clear and troubling things that display a contempt for science and science-based medicine and a desire to use the appearance of scientific methods to gain acceptance for alternative practices. This makes it very likely that approval of the ACVBM as a specialty board would serve as a Trojan horse for the legitimization of other alternative therapies.
5. The potential of herbal medicines would be better explored from a rigorously scientific approach involving specialists in pharmacology, toxicology, nutrition, epidemiology, and other existing medical specialties.

The deadline for public comment on the application is September 1. As this date approaches, there has been more discussion of this issue. The Veterinary information Network (VIN) News Service recently published an article on the debate in which I and other skeptics, as well as several proponents of herbal medicine are quoted at length.

The American College of Veterinary Internal Medicine (ACVIM) has taken a public position opposing the ACVBM application.

Proponents of the application have also been active, including efforts to gain support from the American Holistic Veterinary Medical Association (AHVMA), the leading advocacy group for alternative veterinary medicine . This actually helps to support and illustrate my objection #4 above. Even members of the ACVBM who claim to support a scientific approach and eschew the alternative roots of herbal medicine are providing links to the AHVMA templates for letters supporting the petition. Herbal medicine is still inextricably linked to alternative medicine, and this will not be fixed by setting up a specialty board run by alternative practitioners.

Similarly, the current president of the ACVBM, Dr. Ihor Basko, has made this statement in his appeal to supporters to write letters in favor of the petition:

Surprisingly there is much opposition to the college, mostly from veterinarians. It also appears that the pharmaceutical industry has hired “trolls” disguised as pet owners to write letters in opposition to the college.

Dr. Basko is an advocate of Chinese Medicine and many varieties of unscientific medical practices, and this sort of consipracist nonsense is typical of the ideology and rhetoric of the alternative medicine community. To suggest the ACVBM will be a rigorously and strictly scientific group when practitioners like Dr. Basko dominate the leadership is disingenuous and not convincing.

I encourage anyone dedicated to truly science-based veterinary medicine to write or email the American Board of Veterinary Specialities before September 1 and declare your opposition to this application. I have provided the contact information and a sample letter below:

American Board of Veterinary Specialties
c/o Mr.David Banasiak
1931 N. Meacham Rd, Suite 100
Schaumburg, IL, 60173
DBanasiak@avma.org

Dear Mr. Banasiak:

I am writing to oppose the recognition of the American College of Veterinary Botanical Medicine (ACVBM) as a veterinary specialty organization. The ACVBM does not meet the core criteria set forth by the ABVS, and recognition would not be in the best interests of animal owners nor the veterinary profession.

Botanical medicine is not recognized as a medical specialty, in human or veterinary medicine, in the U.S., Europe, Australia, or most other scientifically advanced nations because the research evidence concerning herbalism and botanical remedies does not support this status. Prescribing practices are largely untested and based on folk medicine beliefs and traditions, and most herbal products are untested and un-regulated. Very few herbal therapies have been validated by the type of high-quality clinical trial evidence typically required for pharmaceutical medicines. Problems with mislabeling and contamination by toxic adulterants and pharmaceuticals is frequently reported for herbal products, with documented harm to patients. While there is great potential for medicinal use of plant-derived compounds, this potential can best be realized through pharmacognosy and other conventional forms of scientific research under the auspices of clinical pharmacology, toxicology, and other existing medical specialties.

The primary distinction the ACVBM offers between its approach and current conventional research and application of herbal remedies is the use of “traditional knowledge” to guide herbal prescribing. This means that the theories and practices of folk medicine traditions are considered sufficient to guide the use of herbal medicines, even when controlled research evidence is unavailable or contradicts traditional theory and practice. Almost none of this “traditional knowledge” has been validated by controlled research, and much of it is incompatible with established scientific principles and knowledge.

Illustrating the reliance of the ACVBM on unscientific principles is the affiliations and practices of the members of the ACVBM Organizing Committee. Nearly all are affiliated with the Chi Institute or other Chinese Medicine organizations, and most are practitioners of Traditional Chinese Medicine (TCM). TCM is an alternative system for understanding health and disease which is entirely independent from, and inconsistent with, science-based medicine. It views disease as arising from imbalances of mystical forces, such as Chi or Yin and Yang, and metaphorical humors such as Wind, Damp, Heat, and so on. Diagnoses such as “Rebellious Chi” or “Excess Wind” are made based on behavioral and historical information, tongue color and texture, pulse quality, and other traditional means. These diagnoses are then used to guide the use of herbal products, which are categorized in their effects by taste, appearance, and historical use rather than any scientific analysis of their components or physiologic effects. TCVM is not a specialty area within scientific veterinary medicine, it is an alternative to it. Recognizing the ACVBM would effectively identify TCM herbalism as a legitimate scientific medical practice without appropriate evidence to support this status.

Additionally, a majority of the ACVBM leadership is also affiliated with the American Holistic Veterinary Medical Association (AHVMA), and many have served in the leadership of this group. The AHVMA promotes and defends every type of alternative medicine, from herbalism and acupuncture to homeopathy and faith healing. Most of the Organizing Committee members promote or utilize numerous alternative therapies other than herbal medicine, and many have been publicly critical of conventional and evidence-based medicine and have recommended greater reliance on traditional knowledge and personal experience. These views do not support a rigorous scientific standard for developing safe and effective therapies and would not promote more evidence-based and higher-quality patient care.

The best way to develop the potential of plant-based medicines is to continue rigorous scientific research into herbal remedies, based on established scientific principles and methods. This progress can best be accomplished through the existing veterinary specialty areas. Traditional use may suggest testable hypotheses, but it is not a reliable guide for prescribing. Recognition of the ACVBM would be counterproductive in encouraging folk medicine-based approaches and in giving the ABVS imprimatur of scientific legitimacy to theories and practices which do not merit it. This would mislead veterinarians and animal owners and encourage the promotion of unscientific alternative practices.

In 2013, I wrote about the burgeoning popularity of the spice turmeric as a medicinal herb. At the time, my conclusions were:

Overall, there is no compelling clinical evidence in humans supporting any use of curcumin or other turmeric compounds…There is virtually no clinical research in companion animals, and what there is does not support claims of benefit from turmeric compounds. Finally, the limited research to date suggests a few potential risks but the significance of these is unclear.

Since then, there have been many additional in vitro or lab animal studies, but no significant clinical trials in companion animal species. The pre-clinical research continues to find interesting biological activity of curcumin and other turmeric compounds which might, or might not, lead to clinically useful effects. At this point, there isn’t much new evidence that supports altering my previous conclusions.

However, one new review has looked at the biologic plausibility of curcumin, which is one factor in assessing the potential medicinal applications. This paper, somewhat surprisingly, suggests that the basic biochemistry of curcumin makes it unlikely to be a clinically useful remedy.

Nelson KM. Dahlin JL. Bisson J. et al. The Essential Medicinal Chemistry of Curcumin J. Med. Chem. 2017;60:1620?1637.

The authors review the pre-clinical and clinical trial literature for curcumin with an eye to features that would make the compound a better or worse candidate medicine. They conclude that its basic biochemical features make it unlikely to be useful but highly likely to generate false positive results if not tested with a clear understanding of its properties:

The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead.

Curcumin…has shown excellent promise in early testing (in vitro), even though this testing may have been bedeviled by design problems that led to several misfires. The structure of 1 suggests that it might be unstable in a biological setting, and in fact, it is: both its in vitro and in vivo stabilities are abysmal…relative to commercial drugs.

To our knowledge, [curcumin] has never been shown to be conclusively effective in a randomized, placebo-controlled clinical trial for any indication. Curcumin is best typified, therefore, as a missile that continually blows up on the launch pad, never reaching the atmosphere or its intended target(s).

While these failures would normally end further research on its use as a therapeutic, they apparently have not deterred researchers interested in its development.

Given its low systemic bioavailability, we remain highly skeptical that an oral dose of 1 can ever be effective in human clinical trials that are translated from reports of in vitro activity… the lack of any observed efficacy of oral curcuminoids in clinical trials where it was given in high doses does not bode well for these alternative hypotheses of therapeutic efficacy.

Unfortunately, no form of curcumin, or its closely related analogues, appears to possess the properties required for a good drug candidate (chemical stability, high water solubility, potent and selective target activity, high bioavailability, broad tissue distribution, stable metabolism, and low toxicity). The in vitro interference properties of curcumin do, however, offer many traps that can trick unprepared researchers into misinterpreting the results of their investigations.

While such an analysis does not entirely preclude curcumin eventually being a useful remedy, it does reduce the likelihood of this, especially given the failure of any dramatic clinical trial results suggesting a significant real-world benefit.

Introduction
In 2010 I first evaluated the Chinese herbal remedy known as Yunnan Baiyao, and I have reviewed additional evidence repeatedly since (1, 2, 3). So far, I have found little reason to believe claims that this remedy can stop bleeding in veterinary patients.

The ingredients are poorly described and not regulated or standardized, as is always the case with Traditional Chinese Medicine (TCM) remedies, and it is unclear if they have all been disclosed since the recipe is consider a commercial secret. TCM remedies have frequently been found to contain toxins and unreported pharmaceuticals, and some YB tested has been found to contain low levels of toxic substances. The TCM theory for how it works, involving movement of blood and mystical and ill-defined entities such as Qi, is inconsistent with established scientific understanding of physiology and blood clotting mechanisms. There are a number of more scientific theories for how the many chemicals in the product might affect bleeding, but none have been properly validated, and it is recommended primarily on the basis of tradition and anecdote.

Of course, despite the implausibility and lack of a clear mechanism, some clinical research has been done. In humans, the most recent review (from a source known to be biased in favor of TCM treatments, c.f. 3, 4) found some evidence of effect but also found that 1) most of the published research was of low quality and high risk of bias, 2) for some conditions the apparent effect disappears when lower quality studies are excluded, and 3) there is evidence of publication bias, in which negative studies remain unpublished creating an inaccurate impression of the true state of the evidence.

Such weak evidence might justify further research, ideally beginning with full identification of components, basic physiologic and pharmacologic studies, and then progressing through pre-clinical studies before clinical trials, as is the appropriate and expected course of investigating new medications. However, the current evidence does not really justify routine clinical use.

There is also some research into Yunnan Baiyao in veterinary species, and I have reviewed this in my previous posts. A couple of new small studies were recently presented at the American College of Veterinary Internal Medicine (ACVIM) annual forum, so I thought it would be worth reviewing those and summarizing the evidence to date.

Recent Studies
MacRae R. Carr A. The Effect of Yunnan Baiyao on the Kinetics of Hemostasis in Healthy Dogs. ACVIM  Forum, National Harbor, MD, 2017.

The goal of this study was to evaluate the effect, if any, of Yunnan Baiyao on laboratory measures of blood clotting and to look for any obvious, short-term adverse effects. Six laboratory dogs were given the product once a day for six days and clotting measures compared before and during the treatment. No harmful effects were reported, and there was no change in any measure of blood clotting.

Adelman L. Olin S. Egger CM. Stokes JE. Effect of Oral Yunnan Baiyao on Periprocedural Hemorrhage and Coagulation in Dogs Undergoing Nasal Biopsy. ACVIM Forum, National Harbor, MD, 2017.

The abstract begins with the statement, “The hemostatic efficacy and safety of Yunnan baiyao (YB) has been demonstrated across multiple species.” This isn’t actually accurate, and it reveals a pretty clear bias on the part of the investigators, which is relevant when looking at the methods and conclusions of the study.

Nineteen dogs having nasal biopsies were randomized to Yunnan baiyao or placebo before having nasal biopsies taken, which commonly causes some bleeding. A variety of outcome measures were evaluated, including laboratory values associated with clotting and assessments of how much blood was lost and how long it took the dogs to clot after biopsy. The report indicates appropriate blinding of investigators, caretakers, and statisticians. However, not all dogs were assessed with the same measures, which introduces some inconsistency and variability into the results.

Time for bleeding to stop- Exactly how this was measured is not described. The YB group ha d a slightly shorter BMBT (300+/- 12 seconds vs 367+/- 9 seconds). Several other variables (age, history of nosebleeds, blood pressure, and number of biopsies taken) were also associated with the BMBT, though the details were not reported.

BMBT (time for bleeding to stop from a standardized cut on the gums)- There was no difference between the groups.

TEG (a lab measure of clotting)- There was no difference between the groups.

Total blood loss- It is also not clear how this was measured. There was no difference between the groups.

Despite the failure to find an effect for most measures and the questionable clinical significance of the one difference seen (a difference from 46 to 88 seconds in the time for bleeding to stop), the authors naturally conclude that the study supports using YB routinely before this type of procedure.

Veterinary Evidence Summary
The table below lists all of the actual in vivo studies in veterinary species I have found. It also lists some key features of these studies that help evaluate how reliable their results are, including the number of animals studied, the use of key methods for preventing bias, such as randomization, blinding, and a control group, and the outcomes.

Table 1. Studies of Yunnan Baiyao in veterinary species.

Of these ten studies, 5 found no effect at all, and 2 others showed mixed results, with possible effects in some measures evaluated in the studies but not in others. Of the three fully positive studies, two did not report any of the major methods for controlling for possible bias and other sources of error.

Overall, this is a very unconvincing set of data. Even clearly ineffective methods can have some positive studies due to bias and error alone, so the lack of a clear, consistent pattern of expected effects is troubling. Not all of the studies used the same measures, so it is possible the product could have some clinical effects by some mechanism that doesn’t affect the laboratory measures of clotting usually used, but that is a big stretch.

It is also worth noting that the studies showing some effect didn’t look find any benefit in terms of clinically important outcomes, such as survival, need for transfusion, etc. Even under the most optimistic assessment of the evidence, it may be that Yunnan Baiyao speeds clotting in the case of small wounds by a few minutes, but this may not necessarily have any meaningful benefit for actual patients.

Bottom Line
The TCM rationale for using Yunnan Baiyao is part of an unscientific, quasi-religious belief system and cannot be accepted as a sufficient basis for using an otherwise unproven remedy on patients, especially when the ingredients in that remedy are not fully disclosed or regulated for quality, consistency, and safety. The more plausible scientific hypotheses for how Yunnan Baiyao might work remain unproven.

The clinical research evidence is mostly negative, and even positive studies have not shown any significant effects on clinically meaningful objective outcomes.  No clear evidence of harm has yet been found, though the limited nature of the evidence does not ensure that the product is truly safe.

References
Ogle CW, Soter D, Cho CH (1977) The haemostatic effects of orally administered yunnan bai yao in rats and rabbits. Comparative Medicine East and West 5:2, 155-160

Ogle CW, Dai S, Ma JC. The haemostatic effects of the Chinese herbal drug Yunnan bai yao: A pilot study. Am J Chin Med (Gard City N Y) 1976;4:147–152.

Graham L, Farnsworth K, Cary J (2002) The effect of yunnan baiyao on the template bleeding times and activated clotting times in healthy ponies under halothane anesthesia. Journal of Veterinary Emergency and Critical Care 12:4; 279; 2002 (abstract only)

Epp TS, McDonough P, Padilla DJ, et al. The effect of herbal supplementation on the severity of exercise-induced pulmonary haemorrhage. Equine and Comparative Exercise Physiology 2005;2:17-25.

Fan C, Song J, White CM. A comparison of the hemostatic effects of notoginseng and yun nan baiyao to placebo control. J Herb Pharmacother 2005;5:1–5

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]

Frederick J, Boysen S, Wagg C, Chalhoub S. The effects of oral administration of Yunnan Baiyao on blood coagulation in beagle dogs as measured by kaolin-activated thromboelastography and buccal mucosal bleeding times. Can J Vet Res. 2017 Jan;81(1):41-45.

Lee A. Boysen SR. Sanderson J. et al. Effects of Yunnan Baiyao on blood coagulation parameters in beagles measured using kaolin activated thromboelastography and more traditional methods. International Journal of Veterinary Science and Medicine. 2017;5(1):53–56.

MacRae R. Carr A. The Effect of Yunnan Baiyao on the Kinetics of Hemostasis in Healthy Dogs. ACVIM  Forum, National Harbor, MD, 2017.

Adelman L. Olin S. Egger CM. Stokes JE. Effect of Oral Yunnan Baiyao on Periprocedural Hemorrhage and Coagulation in Dogs Undergoing Nasal Biopsy. ACVIM Forum, National Harbor, MD, 2017.