Not everything that looks like science really is science. I’ve written about the faux science of some alternative medicine publications, such as the Integrative Veterinary Care Journal, which often publish articles that are held up as scientific evidence for alternative theories but which don’t qualify in any way as scientifically legitimate. And not all science is good science or reliable as evidence. This is, sadly, true of much of the veterinary literature, conventional or alternative. However, alternative medicine publications are particularly vulnerable to poor methodology and creating the appearance of reliable scientific evidence without the substance. A close reading of the literature cited by alternative practitioners to support their claims often finds that the evidence is unreliable or doesn’t actually say what they claim it does (e.g. The Evidence for Homeopathy: A Close Look).
So-called Traditional Chinese Medicine (TCM) (which is, arguably, not traditional at all), is a particularly clear example of this problem. There is an abundance of published research on TCM therapies, especially acupuncture. Most of this is published in China or in TCM-dedicated journals, and it almost always finds exactly what the investigators hope and expect to find. When almost every single research study reports positive results, and when most contain few effective controls for bias, the odds are good that the literature represents the strength of belief among TCM proponents more than the objective truth about the method.
A recent article from the American Journal of Traditional Chinese Veterinary Medicine (AJTCVM) illustrates this problem quite well:
Fowler MP. Deng-Shan S. Huisheng X. A Randomized Controlled Study Comparing Da Xiang Lian Wan to Metronidazole in the Treatment of Stress Colitis in Shelter/Rescued Dogs. AJTCVM. April, 2017.
The AJTCVM is usually not available except to members of the TCVM organization that publishes it, but this article was recently made public. This may be related to the ongoing efforts of the TCVM community to gain recognition for herbal medicine as a board-certified veterinary specialty, but this is just speculation.
This study compares a TCVM herbal remedy to a pharmaceutical for “stress colitis.” The structure of the experiment has many of the hallmarks of traditional scientific clinical research. Unfortunately, the work as a whole does not support the authors inevitable conclusion that the Chines herb is an effective treatment. I will summarize briefly the main problems with the study.
What is “Stress Colitis?”
Unfortunately, this is a commonly used term that does not have a meaningful definition based on established pathophysiology or research evidence. Dogs often develop acute large-bowel diarrhea, with the sort of symptoms described by the authors of this study. This is associated with many possible causes, from parasites to eating unfamiliar or unwholesome substances to changes in routine that are likely a source of psychological and physiological stress. Unfortunately, the term stress colitis is a vague one that can be applied to any acute large bowel diarrhea when no specific cause has been sought or found. In this study, the authors ruled out some common parasites as the cause of diarrhea, but no actual cause was identified. Therefore, the entity they are testing treatments for is ill-defined and could easily be a hodgepodge of different causes.
This wouldn’t be a fatal weakness in itself, so long as objective and consistent criteria were used to identify the problem. However, the criteria for including and excluding patients and for determining whether or not they responded to treatment were subjective and vague as well. This leaves it entirely to the judgement of the investigators whether the dogs had “stress colitis” or not, and whether they got better or didn’t get better with treatment. Such a source of bias is a serious flaw, especially given the lack of any blinding, as I will discuss shortly.
Metronidazole
The authors designed the study to compare the herbal product to metronidazole, a drug commonly used to treat all sorts of diarrhea, including whatever people choose to label “stress colitis.” Unfortunately, there is no scientific evidence showing that this drug is actually effective for acute large bowel diarrhea from most causes, including cases for which no specific cause can be identified. The authors claim the drug is recommended in a commonly used drug handbook, but this is not correct. All the scientific evidence for the use of metronidazole in treating colitis involves chronic, not acute cases, and mostly diseases with an established cause, such as ulcerative colitis, inflammatory bowel disease, and giardia. In other words, the authors cite evidence regarding chronic large bowel diarrhea due to a variety of different causes as evidence for using metronidazole as a treatment for acute large bowel diarrhea of unknown cause (presumed to be related to stress). This misrepresents the evidence.
Metronidazole as a treatment for acute idiopathic large bowel diarrhea is common, but that is an entirely anecdotal practice for which there is no specific scientific support. This means the owners are comparing an untested herb supported only by anecdotal evidence against an untested medication supported only by anecdotal evidence. Not a very robust study for determining the real safety and efficacy of either treatment.
The authors also seem quite ambivalent about metronidazole. On the one hand, they want to identify it as a treatment proven to be effective for stress colitis so they can claim their herbal remedy is effective if it seems to work as well. They state that metronidazole is “typically effective” and is “the drug of choice” for stress colitis. Since the diseases is not clearly defined or understood and the drug actually isn’t proven to be an effective treatment for it (though it is widely used in this way), the implication here is false.
On the other hand, the authors clearly want to emphasize the dangers of conventional therapy so they can make the common claim that their alternative therapy is safer. So only a few sentences after claiming metronidazole is typically effective, they refer to the “poor clinical response” and “ineffectiveness” in some dogs, while then providing a scary list of potential side effects with no discussion of how frequently these actually occur or their relationship to dose or other factors.
Metronidazole does, of course, have risks that have been established by scientific research, as does any treatment with any real effects at all. Nothing works without some risk of unintended effects. However, the risks are generally seen with high doses and long-term use. And while the authors identify no known side effects for their herbal remedy, this is simply because there is virtually no research on this product, and no previous clinical studies at all in dogs. It might be safer or mare risky than metronidazole, but without appropriate research we can’t know. In this study, at least, there were no apparent significant adverse effects. One dog in each group was reported to have vomiting, but whether this was related to treatment is unclear, and there was no difference between the groups and no other possible adverse reactions noted.
Study Design Problems
This study is a classic example of how to set up a study to show what you already believe and want to show. The first author specifically says in the paper that she wanted to run the study because she believes the herb is effective, and may work better than metronidazole, based on her clinical experience. This bias can freely influence the results because there is almost no control for bias in the study. The inclusion and exclusion criteria were subjective, the response to treatment was subjectively measured, and no one was blinded to the group assignment or treatment of any of the dogs. These are not pedantic details but the fundamental core of good, objective science that is absent from this study.
The results of the study seem, not surprisingly, to support the beliefs of the authors. There was no difference in the resolution of diarrhea between the two groups. More than 85% of dogs in both groups got better within 10 days, and the average time to resolution of diarrhea was nearly identical at about 3 ½ days. The authors claim this shows the herb to be just as effective as metronidazole. However, remember that metronidazole has never been actually tested for treating acute large bowel diarrhea, so we don’t actually know if it is effective. What we do know is that in almost every study of acute diarrhea in dogs, most of the dogs get better no matter what we do. Several other studies have shown that more than 80% of dogs with acute diarrhea get better within 3-5 days, just as in this case, with all sorts of other treatments besides metronidazole and the herb used in this study ( e.g. 1, 2). It is very likely that most of the dogs in this study got better regardless of treatment and would have with neither metronidazole nor the herb. The absence of a placebo or no-treatment control group is a serious flaw that makes it impossible for the authors to address this very significant potential explanation for their results.
TCVM Nonsense
It is also important to remember the concept of Tooth Fairy Science. You can design a scientific study to see whether the Tooth Fairy pays out more money depending on the type of tooth lost, the age or sex of the child, and many other variables. You can even do all sorts of fancy statistics to evaluate the results. However, none of this means anything if, as is likely, the Tooth Fairy does not exist.
TCVM is a great example of Tooth Fairy Science. The herb in this study is supposed to be appropriate for cases with “excess pattern of large intestine damp heat” because is can “clear damp heat,” “move Qi,” and “warm middle Jiao.” Since all of the folk mythology of TCVM theory is implausible, untestable, mystical nonsense, the results of controlled studies of it are meaningless. That is not to say the herbs used in TCVM might not have real, and useful biological effects. But these need to be determined by real science, evaluating the chemistry, biochemistry, and pharmacology of these herbs in patients with scientifically defined diseases and measured using appropriate scientific methods. None of this is part of this paper.
The authors suggest that the herb they test has been shown to have benefits for diarrhea, though it has not been clinically tested in dogs before. However, the literature they cite shows only a handful of lab animal studies, which don’t look at anything like acute idiopathic large bowel diarrhea, and a couple of weak studies in humans for, again, quite different problems such as chronic ulcerative colitis. The reality is that despite the attempt to recreate the trappings of science, the authors are basing this study on the pseudoscientific nonsense of TCVM theory, their own personal beliefs and experiences, and anecdotal evidence, not a plausible scientific rationale demonstrated through real research. Tooth Fairy science at its finest.
Bottom Line
This paper illustrates the deep problems in the research literature associated with much of alternative medicine, including TCVM. Implausible therapies are selected according to mystical, pseudoscientific theories and anecdote and then tested inappropriately with little or no serious attempt to control for bias and error, and then the results are overinterpreted to suggest equivalence to conventional treatment or even the superiority of the alternative methods. The body of sloppy and unreliable literature that results misleads not only the public but veterinarians and other scientists into believing there is real reason to take these therapies serious.
This, in turn, supports the deceptive Trojan Horse of integrative medicine, which seeks to blur the real and important distinction between science-based medicine and alternative medicine. Real scientific evaluation of many alternative therapies, especially herbal remedies, needs to be done. This ain’t it. Unfortunately, this is typical of what happens when alternative medicine proponents set out to sue science not to test the reality of their beliefs but to generate marketing tools to sell those beliefs to other clinicians and the public.
Metronidazole does, of course, have risks that have been established by scientific research, >>>>
Antibiotic administration has also been shown to induce
translocation from native commensal bacteria and promote an
inflammatory response (Knoop et al . 2015 ). Metronidazole is a
nitroimidazole antibacterial and antiprotozoal compound rou-
tinely used in the treatment of giardiasis, anaerobic infections
and inflammatory b owel disease (Evans et al . 2003 ). Studies dem-
onstrated reduced colonic bacterial numbers when it was admin-
istered either orally or parenterally (Dion et al . 1980 ). When
administered orally, metronidazole reduces intestinal inflamma-
tion through suppression of cellular immunity, although the exact
mechanism of this action remains to be elucidated (Bijarnason
et al . 1992 ). Metronidazole should be used cautiously because a
recent study showed a significant decrease in aerobic and anaero-
bic bacterial counts in the duodenum of healthy cats, with the
emergence of Streptococcus and Corynebacterium , thereby altering
the commensal flora (Johnston et al . 2000 )
Antibiotic administration has also been shown to induce
translocation from native commensal bacteria and promote an
inflammatory response (Knoop et al . 2015 ). Metronidazole is a
nitroimidazole antibacterial and antiprotozoal compound rou-
tinely used in the treatment of giardiasis, anaerobic infections
and inflammatory bowel disease (Evans et al . &n bsp; 2003 ). Studies dem-
onstrated reduced colonic bacterial numbers when it was admin-
istered either orally or parenterally (Dion et al . 1980 ). When
administered orally, metronidazole reduces intestinal inflamma-
tion through suppression of cellular immunity, although the exact
mechanism of this action remains to be elucidated (Bijarnason
et al . 1992 ). Metronidazole should be used cautiously because a
recent study showed a significant decrease in aerobic and anaero-
bic bacterial counts in the duodenum of healthy cats, with the
emergence of Streptococcus and Corynebacterium , thereby altering
the commensal flora (Johnston et al . 2000 )
Antibiotic administration has also been shown to induce
translocation from native commensal bacteria and promote an
inflammatory response (Knoop et al . 2015 ). Metronidazole is a
nitroimidazole antibacterial and antiprotozoal compound rou-
tinely used in the treatment of giardiasis, anaerobic infections
and inflammatory bowel disease (Evans et al . 2003 ). Studies dem-
onstrated reduced colonic bacterial numbers when it was admin-
istered either orally or parenterally (Dion et al . 1980 ). When
administered orally, metronidazole reduces intestinal inflamma-
tion through suppression of cellular immunity, although t he exact
mechanism of this action remains to be elucidated (Bijarnason
et al . 1992 ). Metronidazole should be used cautiously because a
recent study showed a significant decrease in aerobic and anaero-
bic bacte rial counts in the duodenum of healthy cats, with the
emergence of Streptococcus and Corynebacterium , thereby altering
the commensal flora (Johnston et al . 2000 )
Very interesting topic.
Synthesized metronidazole is suggested to be used only when necessary, due to its potential carcinogenic effects.
Yes, there are some lab animal studies showing carcinogenic potential. however, it is important to realize that the results of feeding studies in mice and rats may not reflect the risks of real-world use, often at much lower dosages, in other species. Even the lab studies conflict, with evidence suggesting different types of tumors may increase in frequency in mice and in rats, and no increase in tumors at all in hamsters. Still, unnecessary use of any drug should be avoided, so the question becomes defining necessary and balancing risks and benefits.
This is such a perfect illustration of why healthcare for both humans and animals is so frustrating. “This aternative medicine has no proven benefits, oh, and neither does this conventional one.”
I came here hoping to learn what I should do to help my dog with a nasty case of post-anesthesia diarrhea. The answer appears to be, as it so often does, that I should do nothing.
Thanks for your good work.
I think you are missing the point. It is frustrating that there are often no 100% definitive, one-size-fits-all answers in medicine. Yet even with this uncertainty, a rational, science-based approach has dramatically improved health and life-expectancy for humans and pets. The method works better than anecdote or trial-and-error, even though it is imperfect. The answer is not “do nothing.” The answer is that you should discuss the options and the relative strength of evidence for all of them and make an informed decision for your pet in concert with your veterinarian.
In a recent clinical trial, dogs with acute diarrhea and no evidence of a specific underlying cause (e.g. parasitosis, endocrinopathy, organ dysfunction, etc.) were randomized to treatment with metronidazole, a commercial probiotic, or a placebo. Based on owner-reported fecal scores, diarrhea resolved in 4.8 +/- 2.9 days in dogs given the placebo, 4.6 +/- 2.4 days in dogs taking metronidazole, and 3.5 +/- 2.2 days in dogs on the probiotic. The differences between groups were not statistically significant.12
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