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

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.

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