The American Holistic Veterinary Medical Foundation: Science or Salesmanship?

Posted on September 26, 2012 by skeptvet

One of the biggest problems with alternative veterinary medicine is the promotion of specific therapies or practices without reasonable scientific evidence that these are safe or effective. Sometimes, the evidence is actually clear that a specific approach is not effective, and yet advocates refuse to acknowledge this and abandon the practice. They often defend such practice on the basis of anecdotal experiences suggesting an effect while ignoring all the reasons uncontrolled observations are often wrong and why miracle stories and other testimonials can’t be trusted. However, sometimes scientific research is used to defend a practice even when the research doesn’t truly validate it.

There are several ways to use science to support a therapy that doesn’t actually work.

1. Extrapolation from tangentially related theories:
Proponents of an untested or demonstrably ineffective method will refer to scientific ideas in unrelated areas to suggest their theories must be true. Quantum physics is commonly relied on in this way since it is complex and not really comprehensible to most of us without facility with advanced mathematics. Homeopaths, have made much of the phenomenon of hormesis to suggest that it validates the ultradilution of homeopathic remedies, though it clearly does not.

The problem with this time of defense is it creates the appearance of scientific legitimacy without actually saying anything substantive about the method being defended.

 2. Extrapolation from pre-clinical research:
In vitro or animal model studies can be very useful in demonstrating a basic concept or in screening for possible safety concerns or other biological effects from a therapy. But what happens in a test tube or a lab mouse is not a reliable guide to what happens when an actual patient, often of a different species, with naturally occurring disease. Such research can generate hypotheses and provide support for them, but it cannot be the primary validation for medical therapies.

Again, the problem is that such research is real, legitimate science used illegitimately to imply that we know more about the effects of a medical therapy than we really do.

3. Low-quality, poorly controlled clinical research:
For some CAM therapies, such as homeopathy and acupuncture, there is an enormous body of clinical research in humans. You would think this would make a decision about whether these therapies work easier, but that isn’t always the case. It has been persuasively argued that most published research is wrong, in conventional as well as alternative medicine. It is very easy to set up an experiment to confirm what you already believe. Even with reasonably good controls, single studies often generate unreliable, usually positive results.

The Decline Effect is a well-known phenomenon in which small, early tests of a hypothesis generate positive results, but as independent investigators get involved and potential sources of error are better understood, the effect of the intervention get smaller and sometimes evaporate altogether. This is how science is supposed to work, but it leads to trouble when early, small, low-quality studies without confirmation by replication are cited as evidence to support a therapy.

The National Center for Complementary and Alternative Medicine (NCCAM) was set up specifically to investigate therapies which had committed believers but had little in the way of plausible theories or preliminary research evidence to suggest they were worth subjecting to clinical trial analysis. Its parent was politics, not science, and after more than 10 years and $1.4 billion, the results have been largely negative and have had little impact on the popularity of CAM therapies, even those shown to be useless. The political figure most responsible for this organization, Senator Tom Harkin, reacted to the negative scientific findings with disappointment and a clear lack of understanding of the purpose and methods of science:

One of the purposes of this center was to investigate and validate alternative approaches. Quite frankly, I must say publicly that it has fallen short. It think quite frankly that in this center and in the office previously before it, most of its focus has been on disproving things rather than seeking out and approving.

Of course, real science doesn’t set out to prove what one already believes but to find out what is true.

Which makes me ambivalent about an initiative by the American Holistic Veterinary Medical Association (AHVMA) to generate funding for alternative veterinary medicine research through the American Holistic Veterinary Medical Foundation (AHVMF).

There are certainly some CAVM therapies which deserve rigorous scientific investigation, particularly in the area of herbal medicine. There are also some that we would be better off without, and if clear scientific evidence that these are useless would lead to their decline in popularity, this too would be a good thing. However, based on both human nature and the example of NCCAM, I am suspicious that the AHVMA efforts are more likely to lead to the promotion of alternative therapies without strong, robust scientific evidence that they are worthwhile.

What is the AHVMF, and what is its purpose? Here’s what the AHVMF web site says:

The Foundation was established to receive and administer funds for research and education in all aspects of integrative medicine, especially as it pertains to that part which is called variously, holistic, alternative, or complementary veterinary medicine, or CAVM. The Foundation concentrates on 3 aspects: scholarships for veterinary students who are interested in this branch of veterinary medicine, research in this aspect of veterinary medicine, and support for the use of and education in this branch in veterinary schools.

So from the beginning, the purpose seems largely about promotion of alternative therapies. Research to investigate objectively the potential value of some specific therapies is certainly appropriate. Supporting students who wish to study these therapies seems a bit premature given the lack of evidence that the therapies themselves have value and deserve to be taught. Likewise, supporting the teaching of CAVM in veterinary schools presumes the value of the methods to be taught. So it is difficult to imagine the AHVMA supporting truly rigorous and impartial research given it seems to be focused primarily on promoting therapies that have yet to demonstrate their worth through such research.

Obviously the AHVMF is an offshoot of the AHVMA, sharing office space and many individuals in leadership positions. The AHVMA is a professional association and lobby for CAVM practitioners, so again this suggests that the AHVMF has been formed as a promotional organization rather than to sponsor truly independent research.

This is further supported by the AHVMF statement specifically about the research aspect of their activities:

Holistic medicine often has answers to chronic disease that use methods with few to no side effects. It may have an answer that is non-existent in conventional medicine. But this type of research is always under-funded and overlooked. The AHVMA Foundation is the best way to bring these modalities into the consciousness of mainstream medical thinking and practice.

Clearly, the starting point for AHVMF-funded research is the proposition that CAVM methods work and research is a useful tool for convincing others of this. This does not suggest a truly critical, open-minded approach to the subject. And if there were any doubt about this, it should be eliminated by the fact that the AHVMF has a page specifically devoted to testimonials for the miraculous benefits of CAVM therapies.

Inspiring stories about patients who have been helped by Integrative Medicine. If you have a story, please send it to us, along with a picture and the name of your veterinarian.

Inspiring stories about the success of specific therapies are not typically found on the web sites of organizations supporting research aimed at finding new or better therapies, such as the American Heart Association, American Lung Association, the National Multiple sclerosis Society, and such. Testimonials are he tool of organizations selling something even if, as in his case, it is not a product but a point of view being marketed.

Organizations like the Bravewell Collaboration and others have been very successful at promoting the integration of unproven or disproven therapies into mainstream medical schools and hospitals by providing financial incentives to hop on the bandwagon. Little good-quality science has resulted, and as mentioned earlier what research has been done hasn’t served to effectively validate much CAM or to discourage the use of methods shown not to be effective.

Obviously, it is impossible and inappropriate to judge in advance the quality of the research the AHVMF claims to be raising money to sponsor. The foundation has already raised over $400,000, a not inconsiderable sum in veterinary medicine, and is aiming for $20 million. I hope these resources lead to good-quality, rigorous studies that will let evidence-based medicine advocates like me accept and begin using new, effective therapies and that will convince CAVM advocates to abandon practices which are shown to be effective despite their a priori beliefs. Perhaps the involvement of veterinary schools will ensure the marketing and promotion activities of the AHVMF don’t damage the integrity of the research it funds. I am skeptical that this will be the case, but I will certainly be watching closely and hoping for the best.

Posted in General | 9 Comments

The Problem with Systematic Reviews of Acupuncture in China

Posted on September 17, 2012 by skeptvet

One of the highest levels of evidence in the system of evidence-based medicine is the systematic review. Unlike narrative reviews, in which an author selects those studies they consider relevant and then summarizes what they think the studies mean, which is a process subject to a high risk of bias, a systematic review identifies randomized controlled clinical trials according to an explicit and objective set of criteria established ahead of time. Criteria are also used to grade the studies evaluated by quality so any relationship between how well studies are conducted and the results can be identified. Done well, a systematic review gives a good sense of the balance of the evidence for a specific medical question.

Unfortunately, done badly systematic reviews can create an inaccurate impression that there is high-level, high-quality evidence in favor of a hypothesis when there really isn’t. Reviews of acupuncture research illustrate this quite well.

Acupuncture is one of the most studied CAM practices, and this means there is a large volume of research to evaluate. While one might expect this to be a good thing, making it easier to tell whether acupuncture is effective for any specific medical problem, the amount of research studies actually makes for muddy waters in which the truth about the clinical efficacy of acupuncture is difficult to discern. The more studies there are, the greater the chance of getting positive results even for an ineffective therapy. If the quality or methodology of the studies is poor, the results will be unreliable. And if numerous studies of questionable quality exist, it becomes easier to generate systematic reviews which appear to provide high-level supporting evidence that doesn’t actually mean what it looks like it means.

For example, a recent systematic review of the use of acupuncture for pain following stroke appeared in the Journal of Alternative and Complementary Medicine.

Jung Ah Lee, Si-Woon Park, Pil Woo Hwang, Sung Min Lim, Sejeong Kook, Kyung In Choi, and Kyoung Sook Kang. Acupuncture for Shoulder Pain After Stroke: A Systematic. Review The Journal of Alternative and Complementary Medicine. September 2012, 18(9): 818-823.

The conclusion seems quite promising; “It is concluded from this systematic review that acupuncture combined with exercise is effective for shoulder pain after stroke.” Given that a systematic review is high-level evidence, this ought to provide us with a fair degree of confidence that acupuncture is useful for this problem.

But a more detailed look casts a bit of doubt on this conclusion. For one thing, 453 studies were identified and only 7 met the quality criteria for inclusion. This suggests that, even in the eyes of acupuncture researchers, most acupuncture research is lousy. And the 7 studies that were evaluated were all conducted and published in China and all showed positive results. This may have as much to do with how research is conducted and published in China as with the efficacy of acupuncture for this problem.

While there is no question that great scientific research is done in China, there is evidence for a systematic problem with the conduct and publication of alternative medicine studies there. Studies reported as randomized are most often not actually properly randomized. And one review in 1998 found that no negative study of acupuncture had ever been published in China. This strongly suggests that the acupuncture literature coming from China is unreliable due to poor methodological quality and a high risk of publication bias.

A review of systematic reviews published in the same journal as the review of acupuncture for shoulder pain also supports a skeptical interpretation of the first paper.

Bin Ma, Guo-qing Qi, Xiao-ting Lin, Ting Wang, Zhi-min Chen, and Ke-hu Yang. Epidemiology, Quality, and Reporting Characteristics of Systematic Reviews of Acupuncture Interventions Published in Chinese Journals.  The Journal of Alternative and Complementary Medicine. September 2012, 18(9): 813-817.

These authors identified and evaluated systematic reviews of acupuncture research published in China and these were their findings:

Results: A total of 88 SRs were identified; none of the reviews had been updated. Less than one third (27.3%) were written by clinicians and one third (35.2%) were reported in specialty journals. The impact factor of 53.4% of the journals published was 0. Information retrieval was not comprehensive in more than half (59.1%) of the reviews. Less than half (36.4%) reported assessing for publication bias. Though 97.7% of the reviews used the term “systematic review” or “meta-analysis” in the title, no reviews reported a protocol and none were updated even after they had been published after 2 or more years.

Conclusions: Although many SRs of acupuncture interventions have been published in Chinese journals, the reporting quality is troubling. Thus, the most urgent strategy is to focus on increasing the standard of SRs of acupuncture interventions, rather than continuing to publish them in great quantity.

This suggest that most systematic reviews of acupuncture published in China don’t search the literature thoroughly and don’t evaluate it properly. Given existing evidence that much of the research being reviewed is itself questionable, there is ample reason to be suspicious of the conclusions of such systematic reviews.

What this means is that when supporters of acupuncture who claim to follow the principles of evidence-based medicine cite systematic reviews, there is a strong possibility that these reviews don’t actually fairly present the balance of the evidence. If they are poor quality reviews based on a biased sample of questionable studies, then they can only serve to create an inaccurate impression of the efficacy of acupuncture.

And there are systematic reviews of the systematic reviews for acupuncture which have found that the balance of the evidence does not suggest a benefit from acupuncture: “In conclusion, numerous systematic reviews have generated little truly convincing evidence that acupuncture is effective in reducing pain.” A large number of studies makes it possible to generate high-level evidence both for and against a hypothesis, in this case concluding both that acupuncture does and does not relieve pain. That only further clouds the issue since naturally everyone cites those reviews which support their a priori position on acupuncture.

Another way of evaluating the state of the evidence on a given intervention is to compare the quality of studies with the likelihood of positive results. Dr. R. Barker Bausell has reviewed the acupuncture this way in his book Snake Oil Science. As it turns out, the highest-quality studies of acupuncture consistently find acupuncture works no better than placebo and that using fake needles and even jabbing the skin in random places with toothpicks work just as well as “real” acupuncture. Lower quality studies are more likely to be positive. This too sheds doubt on the reliability of positive clinical trials

As supporters of acupuncture will undoubtedly point out, this doesn’t prove acupuncture doesn’t work in those conditions for which systematic reviews have stated it does work. It does show, however, that a lot of time, energy, and money has been spent on acupuncture research without generating a consistent body of evidence to support it, which does not justify great confidence.

Which raises the issue of prior plausibility. In theory, I do not object to clinical trial testing of interventions without well-established theoretical foundations. As Sir Austin Bradford Hill, one of the early luminaries of clinical epidemiology, put it, “What is biologically plausible depends upon the biological knowledge of the day.” And as CAM proponents delight in pointing out, sometimes wacky ideas prove true.

What they often fail to acknowledge, though, is that science does a pretty good job of accommodating such things if they can prove themselves through rigorous testing. The theory that Helicobacter could cause duodenal ulcers was considered implausible when proposed in 1982, and it won a Nobel prize for the proponents of the idea in 2005. That’s a pretty quick acceptance of an initially controversial idea, not consistent with the caricature of mainstream science as closed-minded and dogmatic.

In the real world, however, crazy ideas are far more likely to turn out to be wrong than revolutionary. Dr. Sanden’s Electric Belt was at least as wacky as the idea that bacteria cause ulcers, but it has faded into history without any recognition from the Nobel committee. When time, money, and talent are limited (and they always are), spending them on ideas unlikely to bear fruit is hard to justify.

And while a perfect world might allow for thorough, methodical testing of every possible practice, in the real world we owe it to our patients to focus our energies on those ideas most likely to result in real help for them, those ideas which build on established knowledge rather than asking us to ignore or overturn it.

Finally, some sort of reasonable limit on the time and resources committed to investigating an idea is needed. When adequate effort has been made and a strong, consistent body of evidence has failed to emerge, it is time to move on.

In the case of acupuncture, the original theoretical mechanisms invoked to explain why it should help (Ch’i, meridians, and so on) are vitalistic and inconsistent with established science. Attempts to find alternative mechanisms have yielded some interesting information about physiology and the mediation of pain sensation, but they have not turned up a coherent, unified theory of action supported by good evidence. And enormous numbers of clinical trials have been done over decades, again without yielding a consistent body of evidence supporting a specific therapeutic effect for acupuncture beyond the placebo effects of the therapeutic ritual.  

So determining the truth about acupuncture requires more than simply looking for published systematic reviews. The quality of these reviews, and the studies they evaluate, must be critically appraised. And the evidence at all levels, not simply clinical trials, must be considered. Finally, the proposed mechanisms by which acupuncture might work must also be critically evaluated to see if they are supported by good evidence and consistent with established scientific knowledge. It is a misuse of evidence-based medicine to simply conduct poor quality systematic reviews on poor quality trials with a high risk of bias and then take the conclusion of these reviews at face value. A more comprehensive look at the question and the evidence at all levels is required.

 

 

Posted in Acupuncture | 3 Comments

Magic Mushrooms–Can a mushroom-derived compound slow the progression of cancer in dogs?

Posted on September 11, 2012 by skeptvet

There is a recent study out which looks at the potential for a chemical derived from mushrooms to slow the progression of one type of cancer in dogs. It has both strengths and weaknesses, and it is a nice example of both good preliminary, exploratory research and why we shouldn’t put too much confidence in the findings of such research.

Dorothy Cimino Brown and Jennifer Reetz. Single Agent Polysaccharopeptide DelaysMetastases and Improves Survival in Naturally Occurring Hemangiosarcoma. Evidence-Based Complementary and Alternative Medicine. Volume 2012, Article ID 384301, 8 pages. doi:10.1155/2012/384301

The goal of the study was to see if a Chinese herbal medicine product, ImYunity, containing a standardized amount of a chemical called polysaccharopeptide (PSP), had an effect on the progression of the malignant blood vessel cancer hemangiosarcoma (HSA) in dogs. The dogs were those diagnosed with HSA after having surgery to remove their spleens, which were bleeding due to the presence of HSA. Typically, dogs with HSA who have a splenectomy and no other treatment only live a couple of months, though of course there is enough variation that the life expectancy of any individual patient cannot be accurately predicted. Given chemotherapy, these patients tend to live quite a bit longer, however most still do not survive to a year, and all will eventually die from metastatic HSA. Given this poor prognosis even with standard therapy, it is certainly reasonable to investigate alternative approaches.

PSP is believed to be the active compound in some mushrooms used for medicinal purposes, and there is a moderate amount of in vitro and laboratory animal research to suggest the compound may have some effects on the immune system and on cancer cells. I agree with the authors of this paper point out, however, when they say that “as with all other preclinical data, whether these reported findings of suppression of cell proliferation and induction of apoptosis in malignant cells from murine models have relevance in patient care is uncertain.”

Methodologically, the study was of mixed quality. There were only 15 subjects, which is a very small number, and this can lead to random individual variations having a significant effect on any differences seen between groups of subjects. The dogs were selected on the basis of having been diagnosed with HSA and having had their spleens removed. Some had metastases elsewhere in their abdomen at the time of diagnosis and others did not. The dogs were randomly assigned to three different dosage levels of PSP. The investigators and owners were blinded to which dose each dog was getting. However, there was no control group receiving either a placebo or standard therapy.

The two main outcomes studied were time to progression of metastatic disease in the abdomen and survival. While survival is a fairly clear outcome, it is influenced by factors other than the just the progression of the disease since most dogs with cancer are euthanized at their owners’ request. The factors that lead an owner to be ready to do this are many and varied, and not all hinge on the stage of disease in the pet. Still, this is a useful measure in the real world since presumably an effective therapy which slows the progress of disease will be an important factor in determining how long it is before an owner feels it is time to let the pet go.

The second outcome measure is a little less clearly described. An abdominal ultrasound was done on all patients at the time of their enrollment in the study and them monthly thereafter. It isn’t perfectly clear from the report, but it appears that the radiologists performing these examinations were unaware of the treatment each dog was receiving. According to the paper, “Based on this comparison, the board certified radiologist made the determination of progression of metastatic disease.” It’s also not entirely clear what criteria were used to determine progression. How many new lesions or how much growth in established lesions counted as “progression,” and how standardized and consistent was this determination between different radiologists? Such a subjective measure can complicate interpretation of the effect of a therapy.

The results were relatively unimpressive, though some could be consistent with a therapeutic benefit. There was no difference in the median survival among the three groups. However, dogs in the middle and high dose groups lived longer than has previously been reported for dogs with HAS treated only with surgery. This could be consistent with the theory that PSP had some effect on survival.

However, in the absence of an untreated control group, it is at least as likely that this group of dogs differed from those for which survival has previously been reported in some way other than the use of PSP. For example, dogs treated with surgery and not chemotherapy are typically not given any other treatment, and they are certainly not extensively evaluated monthly at a university veterinary hospital. Perhaps the owners who were willing to be a part of this trial were likely to take longer to choose euthanasia than those owners not interested in having their dogs take part for psychological reasons. Or perhaps they generally took better care of their dogs than owners not interested in participating. And it is well know that, for a variety of reasons, people who participate in a research study have better outcomes than those who don’t even if the participants are only getting a placebo, for a variety of reasons. So this result cannot reliable establish that the PSP had any effect on how long these dogs lived.

The other outcome measure, time to progression of abdominal metastases, only showed a statistically significant difference between the high-dose group and the low-dose group. There was no detectable difference between the middle group and either of the others. And the p-value, which establishes how likely this difference was to be due to chance (though not that the difference was due to the treatment), was 0.046. The usual cutoff value for significance is 0.05, so this value was only marginally significant. The difference might be due to an effect of treatment, but it might also be due to chance, especially given the small number of dogs in the trial and the lack of any control groups.

A reasonable interpretation of these results is that this small pilot study found a marginal difference between progression in the high dose group and the low dose, and this could suggest an effect of the drug or could be due to chance, measurement variability, bias, or some other factor. And the survival of the high dose group, which was roughly 6 ½ months compared to the previously reported 3 months for dogs treated with surgery alone (and 6-9 months with chemotherapy), could represent a small benefit from the PSP. Or it could simply be due to random variation or some other, undetected difference between this group of dogs and those studied previously.

Not surprisingly, the authors take a somewhat more positive position on the significance of the results.

While it is necessary to now document more robust and statistically significant differences in an appropriately powered definitive placebo controlled study, it is encouraging that clear patterns and an obvious dose choice emerged from the pilot program.

Based on this data, one could hypothesize that PSP has the potential to have effects on survival similar to that which is seen with standard of care chemotherapy.

Proving, in a biologically aggressive animal model, that PSP delivers antitumor and survival effects in a magnitude similar to that which is seen in standard chemotherapy could have significant implications for shifts in standard of care from current cytotoxic therapies to complementary compounds, such as PSP, that have little to no negative documented effects on normal cells. Most importantly, for those cancer patients throughout the world for whom advanced treatments and cytotoxic therapies are not accessible, CAM, such as PSP as a single agent, could offer benefits to survival and quality of life that are not yet imagined for those populations.

One could hypothesize that PSP is as good as standard chemotherapy for this disease, but that’s only a guess, and this study does little to support that hypothesis. The authors are correct to acknowledge that additional work is needed to demonstrate this is actually true, but they strike a tone that is just a touch more optimistic than these data would seem to justify. Such is inevitable when a researcher has a lot invested in their hypothesis, and it is understandable that the authors would try to put as positive a spin on the results as possible.

However, the suggestion that this therapy, or other alternative therapies, might potentially replace chemotherapy for cancer care is thoroughly unwarranted. For one thing, it has been shown repeatedly than avoiding conventional care in favor of alternative therapies, or even adding these therapies to conventional care, more commonly worsens outcome and quality of life. (see the studies below for a few examples). So it would take a much stronger result than that shown in this paper to even begin to justify the suggestion that alternative therapies could ever be considered a replacement for conventional care.

And the authors also seem to suggest one advantage of PSP as a cancer therapy is the absence of any side effects. No truly effective therapy for a serious disease has ever been found that is free of side effects, so this is an extraordinary hypothesis, which will require extraordinary evidence to prove. Given how unlikely the idea is, it deserves great skepticism and it is ethically questionable to put it forward as an appropriate expectation.

Finally, the authors justify their study partly on the principle that many people cannot afford conventional cancer therapy and that cheaper, possibly safer alternatives should be sought.

A large percentage of [cancer patients] will live in countries that lack the resources for cancer control. The dramatic technological changes that will continue in surgery, radiotherapy, and chemotherapy will lead to increased cure rates; however, these anticipated advances come at a price usually beyond the means of most cancer patients. It is imperative that affordable complementary and alternative treatment strategies, that could considerably reduce the global disease burden at manageable costs, are developed.

There is clear evidence that health and longevity have improved since the advent of a science-based approach to health, and that the benefits of scientific medicine have been greatest in countries which are affluent enough for people to have access to this kind of care (Fig. 1). In poorer countries, people often are forced to rely on traditional folk medicine practices that have not been scientifically validated, and they frequently have poorer health. So there is no question that there is a need to provide better healthcare to people in these countries. There is not, however, any justification for suggesting that alternative medicine, even if rigorously investigated scientifically, will meet this need.

 

This figure shows how life expectancy, one measure of health, has increased as the scientific approac to health has replaced traditional medicine, and how lack of access to scientific medicine is associated with lower life expectancy.

 

For one thing, the reason conventional care is so expensive is largely because tremendous resources are needed to properly develop and research therapies to ensure they are safe and effective. Alternative therapies are largely cheaper because this rigorous scientific study has not been carried out and such therapies are not subject to meaningful regulation requiring evidence of safety and efficacy or verifiable quality control in production and distribution. There is no reason to suppose that if alternative therapies were subject to the same standards of evidence and the same regulatory oversight as conventional medicine that they would be any cheaper.

And it strikes me as ethically questionable to suggest that the proper answer to the healthcare needs of people without access to the best scientific medicine available should be met by putting resources into developing alternative medical therapies for them. These resources would likely be better spent reducing the cost and increasing the availability of therapies already established to be effective. It is perfectly fine to look for additional or better treatments in alternative medicine (subject to reasonable use of plausibility and pre-clinical research to target limited resources efficiently), but the suggestion that such therapies can or should replace conventional care for economically disadvantaged people is not reasonable. There is no good evidence these therapies will be as safe or effective as conventional care or cheaper, so this is a weak justification for research efforts directed at alternative interventions.

Bottom Line
This paper provides an intriguing suggestion that there might be benefit to mushroom-derived PSP for patients with hemangiosarcoma. It is by no means adequate in size or design to demonstrate this to be true, and the results are actually quite weak and as likely to be due to chance or bias as to an actual effect of PSP on this cancer. However, further research into this therapy is certainly justified.

The suggestion that alternative medicine is likely to provide therapies that are as effective as conventional therapy with no side effects is implausible and contradicted by existing evidence. The idea that the proper response to the inadequate availability of proven cancer therapies for economically disadvantaged people is to put resources into investigating alternative medicine and developing a separate set of therapies for these people is an ethically dubious proposition. While investigating such therapies may be appropriate given sufficient evidence to suggest they will prove useful, it would be more appropriate to address healthcare inequities directly rather than justifying such investigation with the goal of developing separate treatments for people with different socioeconomic status.

 

  1. Han E, Johnson N, Delamelena T, Glissmeyer M, Steinbock K. Alternative therapy used as primary treatment for breast cancer negatively impacts outcomes. Ann Surg Oncol 2011;Jan 12 [Epub ahead of print].
  2. John A. Chabot, Wei-Yann Tsai, Robert L. Fine, Chunxia Chen, Carolyn K. Kumah, Karen A. Antman, and Victor R. Grann. Pancreatic Proteolytic Enzyme Therapy Compared with Gemcitabbine-based Chemotherapy for the Treatment of Pancreatic Cancer. Journal of Clinical Oncology. 2010;28(12):2058-63.
  3. Kurian Joseph, Sebastian Vrouwe, Anmmd Kamruzzaman, Ali Balbaid, David Fenton, Richard Berendt, Edward Yu and Patricia Tai. Outcome analysis of breast cancer patients who declined evidence-based treatment.World Journal of Surgical Oncology 2012, 10:118.
  4. Risberg T, Vickers A, Bremnes RM, Wist EA, Kaasa S, Cassileth BR. Does use of alternative medicine predict survival from cancer? Eur J Cancer. 2003 Feb;39(3):372-7.

 

Posted in Herbs and Supplements | 7 Comments

Is Big Pharma Trying to Make CAM More Science-Based or Just Get a Piece of the Action?

Posted on September 9, 2012 by skeptvet

There have been a number of mentions in the media lately of an initiative by GlaxoSmithKline (GSK), one of the biggest of Big Pharma companies, setting up a division in China to study Traditional Chinese Medicine (TCM). Here’s one report quoting a company representative:

Pharmaceutical company GlaxoSmithKline will open a new research unit in China to look at traditional Chinese medicine.

According to the company, Innovative TCM will be one of GSK’s R&D programs in China, aiming to transform TCM from an experience-based practice to evidence-based medicines through innovation and differentiation.

“Traditional chinese medicine is a well-established system of medical practice developed through thousands of years of empirical testing and refinement of herbal mixtures, and relies generally on clinical experience,” said Zang Jingwu, senior vice president and head of R&D China.

“Western medicines, on the other hand, are generally target-based small molecules or biologics, and their approvals for clinical use are based on clinical evidence of safety and efficacy by staged clinical trials,” he said.

He said the newly formed unit is working with academic TCM experts in China to develop new TCM products for the benefits of patients in China and the rest of the world.

The strategy is to integrate the existing TCM knowledge of diseases with modern drug discovery technology and clinical trial methodology.

“We are developing novel therapeutic TCM mixtures as prescription medicines through innovative extraction methods and combinations, and we use clinical data/evidence to differentiate from existing TCM products on the market,” he said.

I have to admit a bit I’m not quite sure how to think about the prospect of this integration of an idiosyncratic and unscientific approach to healthcare with a profit-driven, corporate research and marketing machine. I can spot a few potential problems, though the possibility that something good might come of it is there too.

To begin with, it’s important to remember what TCM is. It is a complex system of looking at health and disease that is vitalistic (based on manipulating spiritual energies not detectable by scientific means), idiosyncratic (not really traditional at all but a set of principles cobbled together in the 20th century from a variety of sources and traditions with some modern innovations tacked on), and, as the GSK representative says, founded on trial and error and individual experiences rather than systematic scientific research. (1, 2, 3, 4) Ultimately, the modern incarnation of TCM as a coherent and comprehensive system of healthcare founded in a philosophical and spiritual world view is fundamentally incompatible with science, which is acknowledged by some practitioners of TCM as well as skeptics. (5)

That doesn’t mean, of course, that some TCM remedies might not be effective. Many of the remedies used are combinations of herbal ingredients, and these unquestionably contain active chemicals that have physiologic effects. The problem is that without controlled research, whether these effects are clinically meaningful, and whether they are beneficial or harmful, isn’t known.

The theoretical system of diagnosis and selection of therapies in TCM is not validated by anything other than anecdote and personal faith, and it contradicts established science, so it is highly unlikely to be accurate or worth investigating. And so far extensive scientific evaluation of acupuncture has failed to find a consistent, meaningful benefit beyond placebo effects. (6, 7). However, rigorous evaluation of the ingredients and combinations of herbal preparations used in TCM might turn up some useful compounds. Certainly, this has been the case for many other drugs derived from plants, though the ultimate use of the drug often bears little relationship to the pre-scientific use of the plant.

There are, of course, some problems even with scientific evaluation of herbal remedies employed in TCM. There is little consistency in the ingredients of particular remedies, with undisclosed substitutions being common, and there is a significant problem with contamination of TCM remedies with parts from endangered plants and animals, toxic metals and even pharmaceuticals (8, 9). So to study such products scientifically, one would first have to clear the hurdle of deciding what the accepted constituents for every given remedy tested really are, and one would have to be very conscious of quality control and not extrapolating results for the product tested to variants identified as the same but not scrupulously evaluated to ensure they actually are the same. Quite a challenge, but perhaps ultimately worth pursuing if the resources and the will are available to do the job properly.

On the other hand, it is important to remember what GSK is. It is a multinational private corporation with enormous financial resources and concomitant influence over governments and the media. It unquestionably produces life-saving medical therapies, but its primary purpose is to make money, and there is no shortage of examples in the pharmaceutical industry of how this can distort the ostensibly humanitarian project of developing medicines.

Perhaps GSK intends to make money by identifying, through rigorous and properly conducted scientific investigation, safe and effective therapies amidst the mélange of remedies currently used according to largely mystical principles in TCM. Or, perhaps GSK intends to cash in on the mystique of TCM, the growing popularity of alternative medicine, and the notoriously weak and ineffectual regulation of the herbal supplement industry to produce products it can sell despite inadequate information about safety and efficacy.

The track record of pharmaceutical companies, and of Chinese food and medicine exporters, in safeguarding the public health is not encouraging. It would be wonderful to see the incredible resources of a company like GSK targeted and a truly scientific evaluation of the potential medicines lurking in TCM remedies. However, just as faith and ideology can distort even honest attempts by alternative medicine proponents to bring scientific scrutiny to their practices, so the potential for profit can distort the efforts of corporations to produce safe and effective medical therapies. There is some evidence that the herbal medicine industry is even less trustworthy than the pharmaceutical industry (10), though I suspect the difference is more that herb and supplement manufacturers are not regulated and watched as closely, not that there is any fundamental difference in the motives, cultures, or practices of large corporations in these two similar industries.

So I will be interested to see whether the growing involvement of conventional pharmaceutical and healthcare companies in the domain of alternative medicine brings more reliable, scientific approach to evaluating TCM remedies (with the necessary rejection of those that fail to prove safe and effective), or if it simply leads to bigger, more aggressive marketing of inadequately evaluated therapies.

Posted in General | 1 Comment

Herbs and Supplements for Pets: What Is a Vet to do?

Posted on September 6, 2012 by skeptvet

I’ve written extensively about herbal remedies and dietary supplements both because these seem among the most likely to be useful of CAM therapies and also because they are widely used despite the lack of good evidence that they are safe and effective in most cases. The success of pharmaceutical medicines and vitamin supplements to treat deficiency diseases has created an expectation that taking a pill can have beneficial effects. When combined with the naturalistic fallacy (that we can identify some things as “natural” and then trust that these are safe) this predisposes people to believe dietary supplements and herbal medicines are good for them.

At least one NIH study suggests that about 18% of adults in the U.S. take some form of “natural product,” that is an herb or remedy that is not a vitamin of mineral. These consist mostly of herbal remedies, with Echinacea, Gingko biloba, garlic, glucosamine, St. John’s Wort, Ginseng, and fish oil being among the most popular. However, there is growing research evidence that these popular products don’t have the health benefits for which most people take them.

Echineacea does not appear to have consistently demonstrable benefits for cold and flu sufferers (1, 2), and there is even less evidence to support other purported benefits (3). The strongest evidence of benefit for Gingko biloba initially was for Alzheimer’s and dementia (4), however two large, long-term clinical trials have failed to support this hoped-for effect (5, 6). I’ve already written repeatedly about the consistent failure of glucosamine to perform better than placebo, and about the equivocal findings for garlic. Ginseng doesn’t perform much better, with mixed results in generally small and not high-quality research studies. (7)

Among the strongest cases for herbal or other “natural” supplements are those made for St. John’s Wort and fish oil. St. John’s Wort does appear to have some benefit for mild depression, though no greater and with no fewer risks than conventional pharmaceuticals, which aren’t themselves always consistently better than placebo (8). Not exactly a ringing endorsement for one of the most intensively studies herbal remedies, to say that it works about as well as the lousy conventional therapies it is meant to replace or complement.

The evidence is better for fish oils, which have shown some consistent, repeatable benefits in clinical studies (9). However, additional recent work has called into question even this widely accepted conclusion (10). I myself have taken fish oil supplements for years, though I have recently decided to skip the capsules and just eat more fish since, as seems to be turning out to be true most of the time, the health benefits associated with eating particular foods don’t necessarily translate into benefits from supplements based on those foods. (For what it’s worth, I also took glucosamine for a while, with no obvious effects, until the evidence against a real benefit became strong enough to convince me I was wasting my money. The key to an evidence-based approach to healthcare is both being open to new ideas and willing to abandon ideas that fail to live up to their early promise). 

So while there is support for using some popular herbal remedies and other supplements, generally the evidence is far weaker than most people suppose. And the Decline Effect is readily apparent in the research on such remedies, with pre-clinical evidence and small, low-quality early trials showing apparent benefit which then gets progressively smaller and often disappears entirely and the amount and quality of the research grows. Promising ideas are worth investigating, but most fail to live up to their promise, so jumping on a new supplement bandwagon early is usually a mistake.

Vitamin and mineral supplements are the other major piece of the supplement market. Unquestionably, there is a real benefit for these in preventing specific nutritional deficiencies. However, the optimal intake of most vitamins and minerals for most individuals isn’t known. Age, sex, lifestyle, health, and many other variables affect how much of what we need to be as healthy as possible, and almost all recommendations to take more of these products than needed to prevent a deficiency are simply made up. General and irrational use of vitamin and mineral supplements not based on specific scientific evidence has consistently proved not only to not be beneficial but in some cases to be actively harmful (11, 12, 13, 14, 15, 16).

Of course, it is a given that people will continue to take supplements even based on flimsy evidence or even when the evidence is clear that benefits are lacking and there is real risk. The desire to control our health through therapeutic rituals, to believe what we wish were true even if it may not be, and the cognitive dissonance involved in letting go of deeply held beliefs when there is strong evidence against them are all factors that make it hard to give up behaviors that we feel, even mistakenly, are beneficial for us. So what should doctors do about our patients’ supplement use?

There is a lack of consistent and coherent policies among regulators and healthcare institutions to help doctors and patients manage the use of supplements concurrently with conventional medical therapies. Many patients (or veterinary clients) don’t tell their doctors about supplement use. Given that these products can interact in dangerous ways with conventional medicines, this present a real risk. So there are a number of things doctors should do, regardless of how favorably or skeptically they view herbal remedies and supplements, to minimize the risks to their patients associated with these products. 

  1. Know What Your Patient is Taking

Doctors should ask their patients or clients about supplement use at every visit. I always ask my clients if their pets are on any medications. If they say “No,” I then ask about vitamins, supplements, herbal remedies, or other healthcare products, and they very often then reveal a whole host of things they are giving their pet.

Despite their belief that these products treat or prevent disease in their pets, these owners don’t think of the products as medicine since that word is generally associated with pharmaceutical products. Only specific and detailed questioning is likely to yield a true picture of what chemicals an owner is putting into their pet’s body. 

  1. Understand the Evidence

We cannot counsel our clients effectively without being knowledgeable about the products they are interested in using. If a supplement or herbal remedy is truly beneficial, we should know this and know how to use it to help our patients. And if such a product presents a danger to our patients, or is simply a waste of our clients’ money, we should know that as well.

Obviously, I am skeptical about the value of many supplements. But I own quite a few references and textbooks about such products which I consult regularly, I maintain a subscription to the Natural Medicines Comprehensive Database, and I make the effort to be informed about the current scientific evidence regarding herbs and supplements (and to make that information available to others through this blog when I can). This seems a crucial part of being a truly useful resource for my clients and patients, even if often I end up having to tell that that the evidence is inconclusive and what they are giving their pets may or may not be in their best interests.

This is not to say that all veterinarians or veterinary students should undergo specialized training in herbal medicine or the use of supplements. All too often, such training is produced by individuals with firm beliefs about the value of such products who recommend them on the basis of historical use, personal experience, or kinds of evidence weaker than, and often in conflict with, the evidence of scientific research. To have an educated, informed, and science-based understanding of supplements does not require one to be trained in their use by practitioners already committed to their worth any more than being an educated, informed, and science-based critic of astrology or homeopathy requires one to train as an astrologer or homeopath.

  1. Communicate Effectively

I see educating and informing my clients as a crucial part of my job. I cannot care for my patients effectively if I cannot communicate effectively with their owners. This means presenting the facts as I understand them, and my informed opinions (which, after all, is what the client is paying me for), clearly and in a way my clients can understand. This also means not taking an adversarial position against the values and beliefs my clients hold. I see it as an ethical duty to tell my clients when I believe they are treating their pets in a way that is useless or harmful, but this message cannot be heard unless it originates from a position of respect for their intentions and their feelings and a shared desire to do what is best for the animal.

My critics would likely be surprised at how many of my clients, with whom I have long-standing relationships of trust and cooperation, utilize therapies that I actively recommend they not use. Disagreement need not lead to personal antipathy, and my clients understand that even when I tell them something they don’t believe or don’t want to hear, I am not challenging their commitment to their pets’ wellbeing or their own competence as an owner.

Veterinarians need to be honest and explicit with their clients about the evidence concerning the therapies we offer and those we recommend against, and we need to not only share what we know but also admit what we do not know. When it comes to counseling clients about the use of supplements, making clear the uncertainty about these products, and that this uncertainty applies to their safety as much as to their purported benefits, is a necessary part of helping our clients make rational, informed decisions about their pets’ care. The biggest problem with the promotion and advertising of such supplements is that they make confident claims well beyond anything even remotely justified by real evidence.

Bottom Line

Overall, there is some reason to hope that some herbal remedies and nutritional supplements will one day be a useful tool in treating our patients. However, even the best-studied of such remedies currently have only weak evidence to support safety and efficacy, and most have nearly nothing but wishful thinking to justify their widespread use, especially in veterinary medicine where good quality clinical trials of such products are almost non-existent.

This means that we need to be aware of the evidence that does exist and explicit with our clients about what it does and does not tell us. And we need to be vigilant in watching out for harm from products that are often mistakenly assumed to be inherently safe. Clearly, such products will continue to be in fairly widespread use until the political climate changes to allow meaningful regulation of them and requirements that they be validated through proper, rigorous scientific study. Until then, veterinarians need to make the effort to be a source of reliable and honest information for our clients in order to protect and care for our patients.

Posted in Herbs and Supplements | 4 Comments

The Harm Complementary and Alternative Medicine Can Do

Posted on August 26, 2012 by skeptvet

What’s the Harm

I have written often about ways in which complementary and alternative medicine (CAM) can be harmful. This is not because I believe CAM is necessarily always unsafe, or that I think conventional medicine doesn’t have significant risks as well. Any therapy that is doing anything at all is likely to have potential risks as well as benefits. It simply isn’t possible to tinker with as complex a system as a living organism without affecting elements of the system one does not intend as well as those one is targeting.

However, the advantage to science-based medicine is that the risks and benefits of individual therapies are often well understood. If we have sufficient information about what an intervention does and what the risks and benefits of it are, we can then make rational choices about using it. The problem with CAM is that there is often very little information about risks and benefits and yet strong claims are frequently made that these therapies work and are safe. The lack of real, scientific information, and beliefs about safety which are not founded on reliable evidence can generate harm.

The two types of harm that can be seen with CAM therapies are direct and indirect. Direct harm is injury or illness experienced by a patient from the treatment itself. This is similar to the side effects one can see with conventional treatment. Indirect harm is the harm that comes from acting on misinformation or false beliefs even when the treatment itself is not dangerous. This usually involves the harm experienced by patients who avoid conventional therapy in favor of unproven or clearly ineffective CAM remedies.

I have put together a list of articles from scientific journals and the news media illustrating both the direct and indirect harm of CAM therapies: What’s The Harm? The name is in honor of the web site What’s the Harm, which is a collection of anecdotes illustrating the dangers of all kinds of pseudoscientific and superstitious thinking, including that behind much of alternative medicine.

This post will be a collection of links to previous posts I’ve written and links to articles elsewhere illustrating the harm CAM can do.

General CAM Use:

Association between CAM use and decreased success of IVF in Holland.

Association between CAM use and decreased survival in cancer patients in Norway.

Boström H, Rössner S. Quality of alternative medicine–complications and avoidable deaths. Qual Assur Health Care. 1990;2(2):111-7.

Yun YH, Lee MK, Park SM, Kim YA, Lee WJ, Lee KS, Choi JS, Jung KH, Do YR, Kim SY, Heo DS, Kim HT, Park SR. Effect of complementary and alternative medicine on the survival and health-related quality of life among terminally ill cancer patients: a prospective cohort study. Ann Oncol. 2013 Feb;24(2):489-94. doi: 10.1093/annonc/mds469. Epub 2012 Oct 30.

Johnson SB, Park HS, Gross CP, Yu JB. Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. JAMA Oncol. Published online July 19, 2018.

Acupuncture

While generally safe if performed by a licensed, properly trained acupuncturist, acupuncture does pose direct risks, including side effects such as dizziness and nausea, infection from improper technique, and trauma from needles.

A Review of Reviews of Acupuncture for Pain: Might Work, Might Not, Could Kill You, Probably Won’t

Veterinary Acupuncture

Cho YP, Jang HJ, Kim JS, Kim YH, Han MS, Lee SG. Retroperitoneal abscess complicated by acupuncture: case report. J Korean Med Sci. 2003 Oct;18(5):756-7.

Choo DC, Yue G Acute intracranial hemorrhage in the brain caused by acupuncture. Headache 2000 May;40(5):397-8.

Chung SJ, Kim JS, Kim JC, Lee SK, Kwon SU, Lee MC, Suh DC. Intracranial dural arteriovenous fistulas: analysis of 60 patients. Cerebrovasc Dis 2002 Feb;13(2):79-88

Cole M, Shen J, Hommer D. Convulsive syncope associated with acupuncture. Am J Med Sci 2002 Nov;324(5):288-9

Ernst E, Sherman K. Is acupuncture a risk factor for hepatitis? Systematic review of epidemiological studies. J Gastroenterol Hepatol. 2003 Nov;18(11):1231-6.

Ernst E. Deaths after acupuncture: A sytematic review. Int J Risk and Safety in Med 2010;22(3):131-6.

Wenju He, Xue Zhao, Yanqi Li, Qiang Xi, and Yi Guo. Adverse Events Following Acupuncture: A Systematic Review of the Chinese Literature for the Years 1956–2010. The Journal of Alternative and Complementary Medicine. E-pub ahead of print. doi:10.1089/acm.2011.0825.

Iwadate K, Ito H, Katsumura S, Matsuyama N, Sato K, Yonemura I, Ito, Y. An autopsy case of bilateral tension pneumothorax after acupuncture. Leg Med (Tokyo). 2003 Sep;5(3):170-4.

Kirchgatterer A, Schwarz CD, Holler E, Punzengruber C, Hartl P, Eber B Cardiac Tamponade Following Acupuncture. Chest 2000 May;117(5):1510-1511

Laing AJ, Mullett H, Gilmore MF. Acupuncture-associated Arthritis in a Joint with an Orthopaedic Implant J Infect 2002 Feb;44(1):43-4

Nambiar P, Ratnatunga C. Prosthetic valve endocarditis in a patient with Marfan’s syndrome following acupuncture. J Heart Valve Dis 2001 Sep;10(5):689-90

Peuker E Case report of tension pneumothorax related to acupuncture. Acupunct Med. 2004 Mar;22(1):40-3.

Saw A, Kwan MK, Sengupta S. Necrotising fasciitis: a life-threatening complication of acupuncture in a patient with diabetes mellitus. Singapore Med J. 2004 Apr;45(4):180-2.

Sun CA, et al. Transmission of hepatitis C virus in taiwan: prevalence and risk factors based on a nationwide survey. Sun J Med Virol 1999 Nov;59(3):290-6

Jayne Wheway, Taofikat B. Agbabiaka, Edzard Ernst. Patient safety incidents from acupuncture treatments: A review of reports to the National Patient Safety Agency. The International Journal of Risk and Safety in Medicine. 2012;24(3):163-169.

Witt CM, Pach D, Brinkhaus B, Wruck K, Tag B, Mank S, Willich SN. Safety of acupuncture: results of a prospective observational study with 229,230 patients and introduction of a medical information and consent form. Forsch Komplementmed. 2009 Apr;16(2):91-7. Epub 2009 Apr 9

Woo PC, Leung KW, Wong SS, Chong KT, Cheung EY, Yuen KY. Relatively alcohol-resistant mycobacteria are emerging pathogens in patients receiving acupuncture treatment. J Clin Microbiol 2002 Apr;40(4):1219-24

Woo PC, Lin AW, Lau SK, Yuen KY. Acupuncture transmitted infections. British Medical Journal 2010;340:c1268.

Yamashita H, Tsukayama H, White AR, Tanno Y, Sugishita C, Ernst E. Systematic review of adverse events following acupuncture: the Japanese literature. Complement Ther Med 2001 Jun;9(2):98-104

 

Chiropractic

There is little research on the risks of chiropractic treatment in dogs and cats (or on any possible benefits). However, there is clear evidence of harm in humans, particularly with manipulation of the neck. Given the limited evidence of benefit (for back pain) in humans and the absence of clear evidence of benefit in veterinary patients, significant caution is warranted. 

Veterinary Chiropractic

SBM–Neck Manipulation:Risk vs Benefit

SBM–Chiropractic’s Pathetic Response to Stroke Concerns

SBM–Chiropractic and Stroke: Evaluation of One Paper

SBM–Chiropractic and Stroke

Albuquerque FC, Hu YC, Dashti SR, Abla AA, Clark JC, Alkire B, Theodore N, McDougall CG. Craniocervical arterial dissections as sequelae of chiropractic manipulation: patterns of injury and management. J Neurosurg. 2011 Dec;115(6):1197-205. Epub 2011 Sep 16.

Herbs and Supplements

Herbs and dietary supplements are among the most plausible and likely to have real physiologic effects of all CAM therapies. This also means, they are the most likely to have potential risks. As things currently stand, most of these products, particularly herbal remedies, should be viewed as drugs that have not been rigorously tested for safety and efficacy (as pharmaceuticals are) and that are not regulated for quality to any meaningful extent (again, unlike pharmaceuticals). Under these circumstances, there are unknown but potentially significant risks to using these products.

Unregulated Herbal Products and Supplements Send 23,000 People to the Emergency Room Annually in the U.S.

FDA Finds Serious and Widespread Violations of Safety and Quality Control Regulations for Dietary Supplements

What’s in Chinese Medicine? New DNA Study Finds Some Unpleasant Answers

Herbal Remedies Can Interfere With HIV Treatment

Less is More—A Reminder of Why Irrational Dietary Supplement Use is a Bad Idea

Neoplasene—Benefits Unproven and Risks Severe

Neoplasene—The Latest head of the Escharotic Hydra

Vitamin Supplements-Do They Prevent Cancer?

GAO Reports on Deceptive Marketing and Contamination of Herbal Products

Risks of Herbs and Supplements Finally Getting Some Attention

Use of Herbals Associated With Lower Quality of Life in Asthma Patients

Orthomolecular Medicine–Big Talk, Little Evidence, Real Risk

GAO Acknowledges FDA Oversight of Dietary Supplements Inadequate 

Consumer Reports—The Dangers of Supplements

Doctor Lies to Dying Cancer Patients about Herbal “Cure”

Vitamins & Supplements

Vitamin C can interfere with chemotherapy.

Unregulated Dietary Supplements Still Killing People

Thomas LK, Elinder C, Tiselius H, Wolk A, Åkesson A. Ascorbic Acid Supplements and Kidney Stone Incidence Among Men: A Prospective Study. JAMA Intern Med. 2013;():1-2. doi:10.1001/jamainternmed.2013.2296.

Vitamin E can increase cancer risk.

Vitamin E not useful for prevention for prostate cancer and can increase risk of congestive heart failure.

Vitamin E supplements increase risk of hemorrhagic stroke

Vitamin E supplements may increase risk of heart attacks and stroke

Vitamin E increases risk of prostate cancer

Vitamin supplements may associated with overall increase in mortality and no benefit in preventing gastrointestinal cancer.

Omega-3 Fatty Acids may increase risk in ventilator patients with acute lung injury

Mursu J, et al. Dietary supplements and mortality rate in older women: The Iowa Women’s Health Study. Archives of Internal Medicine. 2011;17(18):1625-33.

Widespread Failures in Quality Control of Dietary Supplements

Herbal Preparations

Bashir Ahmad, Samina Ashiq, Arshad Hussainb, Shumaila Bashir, Mubbashir Hussain. Evaluation of mycotoxins, mycobiota, and toxigenic fungi in selected medicinal plants of Khyber Pakhtunkhwa, Pakistan. Fungal Biology. 2014;118(9–10):776–84.

Aliye Uc, MD, Warren P. Bishop, MD, and Kathleen D. Sanders, MD, Camphor hepatoxicity. South Med J 93(6):596-598, 2000,

Angers RC, Seward TS, Napier D, Green M, Hoover E, Spraker T, O’Rourke K, Balachandran A, Telling GC. Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis. 2009 May;15(5):696-703.

Angkana R, Lurslurcharchai L, Halm E, Xiu-Min L, Leventhal H, et al. Use of herbal remedies and adherence to inhaled corticosteroids among inner-city asthmatic patients. Annal Allerg Asthma Immunol 2010:104(2);132-138.

Berberine. Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) Chem Res Toxicol 2001 Nov;14(11):1529-34

Cheung E, Ng C, Foote J. A hot mess: A case of hyperemesis. Canadian Family Physician July 2014 vol. 60 no. 7 633-637.

Geller, A. et al. Emergency Department Visits for Adverse Events Related to Dietary Supplements. N Engl J Med 2015; 373:1531-1540

Lauren Blacksell, Roger W. Byard, Ian F. Musgrave. Forensic problems with the composition and content of herbal medicines. Journal of Forensic and Legal Medicine. Volume 23, March 2014, Pages 19–21

Booth JN 3rd, McGwin G. The association between self-reported cataracts and St. John’s Wort. Curr Eye Res. 2009 Oct;34(10):863-6.

Burkhard PR, Burkhardt K, Haenggeli CA, Landis T.Plant-induced seizures: reappearance of an old problem. J Neurol 1999 Aug;246(8):667-70

Chung-Hsin Chen, Kathleen G. Dickman, Masaaki Moriya, Jiri Zavadil, Viktoriya S. Sidorenko, Karen L. Edwards, Dmitri V. Gnatenko, Lin Wu, Robert J. Turesky, Xue-Ru Wu, Yeong-Shiau Pu, Arthur P. Grollman. Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings National Academy of Sciences, April 2012. Panax ginseng: A Systematic Review of Adverse Effects and Drug Interactions. Drug Saf 2002;25(5):323-44 Drug Saf 2002;25(5):323-44

Cupp MJ Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999 Mar 1;59(5):1239-45

Debelle FD, Vanherweghem JL, Nortier JL.Aristolochic acid nephropathy: a worldwide problem. Kidney Int. 2008 Jul;74(2):158-69. Epub 2008 Apr 16.

Douros, A., Bronder, E., Andersohn, F., Klimpel, A., Thomae, M., Ockenga, J., Kreutz, R. and Garbe, E. (2013), Drug-induced acute pancreatitis: results from the hospital-based Berlin case–control surveillance study of 102 cases. Alimentary Pharmacology & Therapeutics.

Emery DP, Corban JG Camphor toxicity. J Paediatr Child Health 1999 Feb;35(1):105-6

Ernst E Adverse effects of herbal drugs in dermatology. Br J Dermatol 2000 Nov;143(5):923-

Fugh-Berman A Herb-drug interactions. Lancet 2000 Jan 8;355(9198):134-8

M.L. Hoang et al., “Mutational signature of aristolochic acid exposure as revealed by whole-exome sequencing,” Science Translational Medicine, 5: 197ra102, 2013.

Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol. 1997 Apr;37(4):344-50

Kutz GD. Herbal dietary supplements: Examples of Deceptive or questionable marketing practices and potentially dangerous advice. General Accounting Office. May 26, 2010.

Lai MN, Lai JN, Chen PC, Tseng WL, Chen YY, Hwang JS, Wang JD. Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid. Nephrology (Carlton). 2009 Apr;14(2):227-34.

Lawrence JD. Potentiation of warfarin by dong quai. Page RL 2nd, Pharmacotherapy 1999 Jul;19(7):870-6

Mangala, P. Study of Lead Content in Ayurvedic and Homeopathic Medicines Commonly Used for the Treatment of Cold, Cough & Body Aches. IOSR Journal Of Environmental Science, Toxicology And Food Technology. 2014;5(3):8-12.

Means C. Selected herbal hazards.Vet Clin North Am Small Anim Pract 2002 Mar;32(2):367-82

National Toxicology Program. Technical Report on the Toxicology and Carcinogenesis Studies of Gingko Biloba extract in F344/N Rats and B6C3F1/N Mice. March, 2013.

Victor J. Navarro, Huiman Barnhart, Herbert L. Bonkovsky, Timothy Davern, Robert J. Fontana, Lafaine Grant, K. Rajender Reddy, Leonard B. Seeff, Jose Serrano, Averell H. Sherker, Andrew Stolz, Jayant Talwalkar, Maricruz Vega, Raj Vuppalanchi. Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network. Hepatology; Article first published online: 25 AUG 2014 DOI: 10.1002/hep.27317

Steven G Newmaster, Meghan Grguric, Dhivya Shanmughanandhan, Sathishkumar Ramalingam, Subramanyam Ragupathy. DNA barcoding detects contamination and substitution in North American herbal products. BMC Medicine 2013, 11:222

Nizsly N, Grizlak B, Zimmerman M, Wallace R. Dietary Supplement Polypharmacy: An Unrecognized Public Health Problem? eCAM 2010 7(1):107-113

Norred CL, Finlayson CA Hemorrhage after the preoperative use of complementary and alternative medicines. AANA J 2000 Jun;68(3):217-20

O’Connor A, Horsley CA. Yates, KM “Herbal Ecstasy”: a case series of adverse reactions. N Z Med J 2000 Jul 28;113(1114):315-7 Pittler MH.

S.L. Poon et al., “Genome-wide mutational signatures of aristolochic acid and its application as a screening tool,” Science Translational Medicine, 5: 197ra101, 2013.

Ernst, E Risks associated with herbal medicinal products. Wien Med Wochenschr 2002;152(7-8):183-9

Poppenga RH.Risks associated with the use of herbs and other dietary supplements. Vet Clin North Am Equine Pract. 2001 Dec;17(3):455-77, vi-vii

Pies R Adverse neuropsychiatric reactions to herbal and over-the-counter “antidepressants”. J Clin Psychiatry 2000 Nov;61(11):815-20

Prakash S, Hernandez GT, Dujaili I, Bhalla V. Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease. Nat Rev Nephrol. 2009 May;5(5):297-300.

Raman P, Patino LC, Nair MG. Evaluation of metal and microbial contamination in botanical supplements. J Agric Food Chem. 2004 Dec 29;52(26):7822-7

Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G Acute heart transplant rejection due to Saint John’s wort. Lancet 2000 Feb 12;355(9203):548-9

Saper RB, Phillips RS, Sehgal A, Khouri N, Davis RB, Paquin J, Thuppil V, Kales SN. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet. JAMA. 2008 Aug 27;300(8):915-23.

Shad JA, Chinn CG, Brann OS Acute hepatitis after ingestion of herbs. South Med J 1999 Nov;92(11):1095-7 Smolinske SC J Am Med Womens Assoc 1999 Fall;54(4):191-2Dietary supplement-drug interactions.

Tachjian A, Maria V, Jahangir A. Use of herbal products and potential interactions in patients with cardiovascular disease. J. Am. Coll. Cardiol. 2010 55: A32 ,

H.-H. Tsai, H.-W. Lin, A. Simon Pickard, H.-Y. Tsai, G. B. Mahady. Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. International Journal of Clinical Practice, 2012; 66 (11):

Wang JD, Lo TC, Chen PC. Increased mortality risk for cancers of the kidney and other urinary organs among Chinese herbalists. J Epidemiol. 2009;19(1):17-23. Epub 2009 Jan 22.

Zhang SY, Robertson D. A study of tea tree oil ototoxicity. Audiol Neurootol 2000 Mar-Apr;5(2):64-8

Posted in Topic-Based Summaries | 13 Comments

Veterinary Acupuncture

Posted on August 26, 2012 by skeptvet

What is it?

Because of the wide variety of theories, approaches, and specific practices acupuncturists use, it is difficult to find agreement as to what exactly acupuncture is. At its core, acupuncture is the practice of inserting needles into the body in an attempt to relieve suffering, treat disease, or improve the quality of a patient’s life.

Though needling and other interventions at points on the body have been practiced in various cultures around the world, acupuncture today is usually associated with needling practices that originated in China. Some acupuncturists claim that they base their treatments on the Chinese concept of Ch’i, which is usually described as a vital force which flows through channels in the body (often called meridians). These practitioners may also claim that imbalances or blockages of Ch’i can cause disease, which can then be treated by inserting needles into meridians at specific points. Ch’i is not detectable by any known means, and neither acupuncture points nor meridians can be identified as physical structures in the body or through any kind of medical imaging.

Other acupuncturists disavow mystical concepts such as Ch’i and claim their treatments work by stimulating release of natural pain control chemicals, such as endorphins, or by affecting blood flow, the function of nerves, and other scientific physiological means. However, none of these proposed mechanisms are supported by any consistent research evidence.

Still other schools of acupuncture claim that the entire body can be mapped onto one part, such as the hand (e.g. Korean Hand Acupuncture) or the ear (a system developed in France in the 1950s), and that needling or other manipulations of points in this location can affect distant organs. Again, no identifiable connections between these proposed local maps and distant organs have been found.

The number and location of acupuncture points has changed often through history, and today there is great variety among acupuncturists as to the sites used. In fact, some proponents of acupuncture, including Felix Mann, past president of the British Acupuncture Society, deny that specifically identifiable point for applying acupuncture exist at all.

In addition to needle insertion, some acupuncturists burn herbs at acupuncture points, pass electric current through the needles or pads placed on the skin, massage or inject vitamins at acupuncture points, or use laser light or other methods to treat patients. Thus, there is no agreement among proponents of acupuncture about the underlying basis for the practice, the specific points to be used, or how these points are to be stimulated.

The popularity of acupuncture has risen and fallen many times in China and the West. After being largely replaced in China by Western medical practices in the 19th and early 20th centuries, the practice underwent a resurgence in the 1950s and 1960s, as an effort by the Communist Party to provide cheap health care in places without modern facilities or trained doctors. It has since become a relatively minor element of medical care in China among those with access to more popular, Western scientific medical. The current interest in acupuncture in Europe and the United States began in the 1970s, following the reopening of China to outsiders.

Historically, acupuncture as understood today was never applied to animals in China. Other interventions, such as bleeding or burning herbs at points on the skin were practiced on animals, but animals were considered fundamentally different from humans in ways that made the methods which have since been developed into modern acupuncture inappropriate for veterinary patients.

Nevertheless, with the rise in interest in acupuncture in the West during the 1970s, the acupuncture points in use for animals today were invented by Western practitioners extrapolating from charts made for humans. The logic of this is sometimes questionable, as for example in the use of a “gallbladder meridian” for acupuncture treatment in horses despite the absence of a gallbladder in this species. As with humans, there is no consistency among acupuncturists as to the rationale for therapy or the specific points or methods to be used.

Does It Work?

There is an enormous amount of scientific research devoted to acupuncture in humans. As always, some studies support its use and others find no evidence of benefit. It can be difficult to sort out the real answer from this confusion.

Studies performed by proponents of acupuncture or published in journals devoted to the practice are almost always positive. Studies performed by critics or neutral researchers are generally negative or inconclusive. Furthermore, as with any medical therapies, negative studies on acupuncture are less likely to be published since they are disappointing to the researchers and not attractive to journals, so there is some inherent bias in the literature for positive results. This is especially true in China, where many of the studies of acupuncture have been published and where 98% of all medical studies published (and 100% of studies in alternative methods such as acupuncture) report positive results.

The best quality scientific studies require blinding, where the patients and researchers not know whether each subject is getting the real acupuncture treatment or a fake (placebo) treatment. Unfortunately, it can be very difficult to fool a person about whether or not they are receiving real or fake acupuncture, and it is impossible to fool the acupuncturist doing the treatment.

Many other factors complicate interpretation of human clinical trials. Confidence in the results can only come from consistent, repeatable outcomes of many well-designed trials conducted by different investigators. However, despite decades of studies in acupuncture, there is still no such body of evidence that shows acupuncture to be consistently effective for any condition.

When the best quality studies, with reasonable numbers of subjects and good controls for bias, are reviewed they find no benefit from acupuncture for most conditions. The evidence is mixed or shows some benefit for some types of chronic pain, and for nausea following chemotherapy or surgery. The largest, best designed, and most recent studies have found that sham or fake acupuncture (using random locations or not actually puncturing the skin with the needles) seems to have about the same benefit as real acupuncture treatment. And patients who believe they are getting real acupuncture even when they aren’t get more relief than those who actually get acupuncture but think they are getting the placebo treatment. The degree of benefit, when any is seen, is generally very small and considerably less than most conventional therapies when these are used for comparison.

So the evidence for humans indicates that acupuncture may make people with chronic pain or nausea feel more comfortable, though this is probably due to altering their perception or awareness of the discomfort rather than actually treating the source of the discomfort in the body. This may have some benefit as an adjunct to traditional scientific medical treatment.

Does it work for animals? This would seem to be easier to determine than it is for humans because no effect from the patients’ attitudes or beliefs would be expected in animals. However, it is currently impossible to determine if there is any benefit of acupuncture for veterinary patients because of the lack of well-conducted research studies. The quality of the acupuncture studies that have been done in veterinary medicine is generally very low. A recent systematic review in the Journal of Veterinary Internal Medicine found so few controlled trials of such poor quality that despite reports of benefit from acupuncture in some studies and no benefit in most, the authors concluded that “there is no compelling evidence to recommend or reject acupuncture for any condition in domestic animals.”

For now, we can only say that it appears somewhat helpful for subjective discomfort, such as pain or nausea, in humans, especially if the patient believes it will be helpful. The evidence is not available to say with certainty whether it is helpful to veterinary patients, but the apparent importance of patient attitudes or beliefs for benefit in humans make it doubtful that animals will experience the same benefits, since their experience is unlikely to be affected by such factors. However, the caretakers of veterinary patients, who evaluate the effectiveness of therapy and make medical decisions for the patients, can be influenced by their own experiences and beliefs, which makes objective assessment of the effect of acupuncture in the clinical setting very difficult.

Is it Safe?

The incidence of complications from acupuncture in humans is low. It has been reported to cause minor local pain and bleeding fairly commonly. More serious side effects, including fainting, vomiting, hepatitis, permanent nerve damage, and death from collapsed lungs have been reported, but these appear to be extremely rare. Adverse effects of acupuncture in animals have not been reported in the sparse literature that exists on the subject.

Summary

  • There is no evidence for the reality of the more mystical principles underlying some acupuncture practices, such as Ch’i, yin/yang, specific acupuncture points, or meridians. There is also no verifiable way to locate or identify specific locations for applying acupuncture.
  • More scientific concepts, such as endorphins and neuronal gating, are at least potentially testable, but as yet the evidence does not show that these explanations justify the clinical use of acupuncture.
  • In humans, acupuncture may have some benefits for reducing the perception of chronic pain and nausea, but it is doubtful that our animal patients will experience this same benefit since it seems to be highly dependant on what the subject believes about their condition and treatment. There is no consistent evidence for a benefit in the outcome of any disease in humans treated with acupuncture.
  • In animals, there is no reliable, high-quality research evidence for the benefits of acupuncture. The studies that have been done have found both positive and negative results, but the poor quality and lack of replication make the existing evidence insufficient to recommend acupuncture therapy.
  • Acupuncture is unlikely to be harmful to most patients.
  • With very little risk of harm, and no convincing evidence of benefit, the use of acupuncture in animals should be seen as an experimental adjunct to conventional therapy, not a replacement for proven medical treatments.

References and More Information
Barker Bausell, R., Snake Oil Science: The Truth About Complementary and Alternative Medicine, Oxford University Press, 2007

Ernst, E., White, A.R., Prospective studies of the safety of acupuncture: a systematic review. Am J Med Apr 2001;110(6):481-5

Habacher, G., Pittler, M.H., Ernst, E., Effectiveness of acupuncture in veterinary medicine: systematic review. J Vet Int Med May-Jun 2006;20(3):480-8.

Mann, Felix. Reinventing Acupuncture, Butterworth Heinemann, 1992

Ramey, D., Rollin, B., Complementary and Alternative Veterinary Medicine Considered, Iowa State Press, 2004

Sing, S., Ernst, E., Trick or Treatment: The Undeniable Facts About Alternative Medicine, W.W. Norton & Company, 2008

The Cochrane Collaboration, The Cochrane Reviews, a searchable database of systematic reviews of the human medical literature at http://www.cochrane.org/reviews/

 

Posted in Acupuncture | 11 Comments

The Danger of Choosing Alternative Therapies over Conventional Care

Posted on August 26, 2012 by skeptvet

One of the most common responses to criticisms of alternative medicine is that, whether it is effective or not, at least it can’t do any harm. There is ample evidence, unfortunately, that this is not true. Any therapy with a potential benefit also has potential harms, so if CAM interventions do anything at all, one would expect some side effects. But even for those that are completely ineffective, there are risks.

Some of these risks are direct. Herbal remedies and supplements can be toxic or contain toxic contaminants (1, 2, 3). And other CAM therapies can be directly harmful, such as chiropractic (4), herbal remedies (5), and even acupuncture (6). But even for therapies that are inherently safe because they contain no active ingredients, such as homeopathy (7), there are indirect risks. Avoiding effective conventional therapies because of a false belief in the value of alternatives can lead to significant harm. A new study illustrates this in women with breast cancer.

Kurian Joseph, Sebastian Vrouwe, Anmmd Kamruzzaman, Ali Balbaid, David Fenton, Richard Berendt, Edward Yu and Patricia Tai. Outcome analysis of breast cancer patients who declined evidence-based treatment.World Journal of Surgical Oncology 2012, 10:118.

This study compared the survival of women diagnosed with breast cancer for those who accepted standard medical care and those who did not. The authors concluded:

A total of 185 (1.2%) patients refused standard treatment…The 5-year overall survival rates were 43.2% (95% CI: 32.0 to 54.4%) for those who refused standard treatments and 81.9% (95% CI: 76.9 to 86.9%) for those who received them. The corresponding values for the disease-specific survival were 46.2% (95% CI: 34.9 to 57.6%) vs. 84.7% (95% CI: 80.0 to 89.4%).

Women who declined primary standard treatment had significantly worse survival than those who received standard treatments.

Of the women who declined care, 54% pursued some form of alternative therapy instead, and overall 5-year survival for this group was 57.4% (95% CI: 42.7 to 72.1%).

It is important not to over interpret these results. To begin with, the number of women who refused standard treatment was very small, which suggests that most understand the value of conventional therapy for this disease. And of those who refused treatment, many may have done so for reasons having nothing to do with their beliefs about conventional versus alternative therapies. There are many perfectly sound reasons for choosing not to pursue treatment depending on the extent of disease, the chances of benefit and harm from therapy, and personal circumstances and values. No clear reason was given for almost half of the women who refused, so it is impossible to know whether or not CAM played any role in their decision or their outcomes.

And choosing CAM instead of conventional therapy may not have been the only reason for the difference in survival between women who did or did not have standard treatment. Women who were sicker, had more advanced disease, or had other diseases as well may have been less inclined to pursue therapy, and also more likely to die sooner than women with a better chance of a good outcome with standard treatment.

And women who pursued CAM therapy instead of standard treatment did do slightly better than women for whom no reason for refusing traditional care was given (57.4% 5-year survival versus 43.2% 5-year survival). This would make sense if women who refused all care, even CAM, did so because they had more aggressive or advanced disease or other health problems.

However, there is no question that women who chose standard treatment did far better than those who choose CAM. The difference in 5-year survival between CAM (57.4%) and standard care (81.9%) was huge and unequivocal. And while the specific CAM used was not known in each case, overall there is no reason from these data to believe CAM in general has anything like the efficacy of conventional breast cancer treatment. If there is some form of CAM that performs as well as conventional care, no one has yet presented the data to show this, so claims that this is a legitimate alternative and that refusing standard care is a reasonable choice for women who want to treat their disease are not supported by any evidence and are, in fact, contradicted by the evidence of this and other similar studies (8, 9)

This is yet another study which emphasizes that importance of not substituting unproven alternative therapies for science-based medical care. While investigating the possibility that some plausible alternative therapies may have benefit is reasonable, choosing CAM over standard care is not and is likely to result in real harm.

Posted in General, Miscellaneous CAVM | 2 Comments

The Pseudoscience of Veterinary Chiropractic

Posted on August 19, 2012 by skeptvet

The defining characteristic of pseudoscience is an idea which sounds scientific, which claims to be scientific, but which isn’t actually based on legitimate scientific research or is theoretically inconsistent which established scientific knowledge. There can be some subjectivity in the characterization of something as pseudoscience, and of course no one promoting an idea would ever accept the label for their own beliefs. However, an article I recently read concerning veterinary chiropractic exemplifies many key features of a pseudoscientific idea.

Maler, MM. Overview of veterinary chiropractic and its use in pediatric exotic patients. Vet Clin Exot Anim. 2012;15:299-310

The article spends a great deal of time describing the Vertebral Subluxation (VS), which the author states “is at the core of chiropractic theory, and its detection and correction are central to chiropractic practice.” The only problem with this claim is that the vertebral subluxation, as defined by chiropractic theory doesn’t exist. (1, 2, 3)

Historically, chiropractors defined the VS as a misalignment of bones in the spine, leading to interruption in the flow of “innate intelligence,” a magical spiritual force responsible for normal health. Of course, no scientific evaluation of such a supernatural force is possible, and to gain the appearance of scientific legitimacy, most chiropractors gradually moved away from this concept and argued that the misalignment of vertebrae damaged health by impinging on nerves leaving the spine. This theory makes some sense when used to explain musculoskeletal pain, though it doesn’t make any sense when used to justify chiropractic as a treatment for ear infections, asthma, allergies, or other such complaints.

As it turned out, however, chiropractors have never been able to demonstrate that the bones they are supposedly adjusting into proper position were ever out of position. In other words, they have never been able to show any misalignment in the spine treatable by their form of manipulation. Studies involving imaging, such as x-rays, don’t show the misalignments, and when radiologists or chiropractors look at x–rays of patients diagnosed with a VS on physical examination, they can’t consistently find a lesion in the area identified as abnormal during the exam.

In response to this failure, chiropractors have once again modified the definition of the VS, this time describing the subluxation not as a misalignment of bones but a “a complex of functional and/or structural and/or pathological articular changes that compromise neural integrity and may influence organ function and general health.” How’s that for a definition vague enough to qualify as a horoscope? Basically, chiropractors are now saying that a VS cannot be seen or measured or identified in any way other than the subjective impression of a chiropractor during an examination, yet it is still an appropriate basis for an entire approach to maintaining health and treating innumerable diseases.

But the situation is even worse than it sounds. When chiropractors examine the same patient multiple times, they cannot consistently locate a VS in the same location each time. And when multiple chiropractors examine the same patient, they all claim to find abnormalities in different places. So they can’t even agree with themselves or each other on where a VS is in any particular patient. Again, it is hard to imagine such a nebulous entity being the foundation of comprehensive healthcare approach, much less one claimed to be scientific in its foundations.

To their credit, a growing minority of chiropractors recognize that the VS is a myth and seek to identify legitimate, scientific explanations for the limited but well-demonstrated benefits of chiropractic therapy in treating lower back pain. Such evidence-based chiropractors have been trying to reform their profession since the 1960s, with pretty limited success. Some of the most conclusive evidence against the existence of the VS comes from chiropractors themselves applying truly scientific methods to the evaluation of this pseudoscientific concept.

A review of the literature which appeared in a chiropractic journal in 2009 evaluated the research evidence concerning the VS to see if it met standard criteria for a cause-effect relationship between the VS and disease.

Miritz TA. Morgan L. Wyatt LH. Greene L. An epidemiological examination of the subluxation construct using Hill’s criteria of causation. Chiropr Osteopat 2009;2:17-13.

The criteria for causation in epidemiology are strength (strength of association), consistency, specificity, temporality (temporal sequence), dose response, experimental evidence, biological plausibility, coherence, and analogy. Applied to the subluxation all of these criteria remain for the most part unfulfilled.

There is a significant lack of evidence to fulfill the basic criteria of causation. This lack of crucial supportive epidemiologic evidence prohibits the accurate promulgation of the chiropractic subluxation.

The fact that in over 100 years since the beginnings of chiropractic no one has been able to demonstrate the existence of the foundational concept for the method, the vertebral subluxation, doesn’t prevent the author of the veterinary clinics article from describing it in detail, with diagrams and lots of scientific terminology. She then goes on to make a wide variety of therapeutic claims, identifying chiropractic as a successful intervention for disease in exotic species.

As evidence for these claims, she cites quite a few textbooks and other writings of her fellow chiropractors, but virtually no relevant clinical trials. The author acknowledges this lack of research support but, in a technique common among practitioners of unproven approaches, she places the blame for this everywhere except on the chiropractic community:

Chiropractic research is in it’s infancy compared to traditional medicine largely due to lack of funding and proprietary interest in chiropractic as well as historical staunch opposition from the American Medical Association and other medical groups.

For a treatment approach that has been in existence for a century, with 50,000 licensed chiropractors in the U.S. alone, and with annual revenue for chiropractic treatment estimated at $10 billion in the U.S., it is hard to justify failing to subject the practice to rigorous scientific scrutiny due to lack of funds.

And while there once was organized opposition to chiropractic on the part of the American Medical Association, this vanished after an antitrust lawsuit finally settled in 1987. The judge found that while the AMA had a legitimate concern about the unscientific nature of chiropractic and the inadequate evidence for safety and efficacy, it did not have the right to organize a boycott against the practice. Organizations representing conventional healthcare providers have done nothing to stop chiropractors from pursuing rigorous scientific evidence to support the theory of the VS or the safety and efficacy of chiropractic treatment.

Yet despite all of that, the only convincing evidence that has emerged to support chiropractic treatment is in the care of humans with lower back pain, in which chiropractic is about as effective as conventional care. This does not justify the application of chiropractic for any other medical condition or the use of chiropractic in non-human animals without appropriate research to justify this. And it certainly does nothing to support the pseudoscientific nebulosity that is the vertebral subluxation. As long as chiropractors cling to this notion and make claims for their practices beyond what is justified by real evidence, the practice will continue to be a pseudoscientific one.

Posted in Chiropractic | 2 Comments

Ozone Therapy for Pets

Posted on August 12, 2012 by skeptvet

I’ve recently run across some advertising for the wonders of ozone therapy in pets. This is a treatment that hasn’t caught on much in veterinary medicine (fortunately), but I thought I’d take a look at it before it becomes the next big fad.

What Is It?
According to the Food and Drug Administration (FDA),

Ozone is a toxic gas with no known useful medical application in specific, adjunctive, or preventive therapy. In order for ozone to be effective as a germicide, it must be present in a concentration far greater than that which can be safely tolerated by man and animals.

According to the Environmental Protection Agency (EPA),

ozone is an air pollutant that is harmful to breathe and it damages crops, trees and other vegetation. It is a main ingredient of urban smog.

Ordinary oxygen gas consists of two oxygen atoms bound together, hence its chemical name O2. Ozone contains three oxygen atoms (O3), and is very reactive, breaking down spontaneously and combining readily with other chemicals. These oxidation reactions are the reason ozone can be used as a disinfectant, killing microorganisms through production of oxidative free radicals.

Proponents of ozone therapy claim that it can be medically beneficial in several ways. Its ability to kill microorganisms and other living cells has been claimed to make it useful for treating infectious diseases and cancer. It is also thought by some to increase the amount of oxygen available to tissues, which may be useful in preventing or treating disease, and to stimulate or modify the immune system in a beneficial way.

Ozone is employed in medical applications in multiple ways, including direct injection into blood, muscle, joints, or body cavities, autohaemotherapy (removing blood from the patient, exposing it to ozone, and then returning the blood to the patient’s body), insufflation of the rectum, vagina, or other body spaces with ozone gas, administration of ozone treated water or saline, and topical application of ozone gas or ozone-treated substances.

Does It Work?
There are pre-clinical, in vitro, studies of ozone applied to infectious organisms and cancer cells and demonstrating it can kill these. As I have often pointed out, however, so can bleach, hydrochloric acid, and many other substances which are not appropriate to give to patients as a form of therapy. A few animal model studies have also suggested a benefit in cancer treatment.

Several reviews have found little controlled clinical research showing beneficial effects in patients treated with ozone therapy. Here are some of the conclusions from these reviews:

Ozone’s use in medicine has been debated for decades, but references to its use were sporadic in the major medical journals. Most of the claims of its efficacy were anecdotal…Current data on the usage of ozone therapy as therapeutic options for various health conditions lacks sufficient safety and therapeutic advantage over available conventional therapeutic modalities…There is insufficient clinical evidence to recommend ozone therapy as a form of alternative treatment….(Health Technology Assessment Report: Ozone Therapy, Ministry of Health, Malaysia, December, 2005)

Given the high risk of bias in the available studies and lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care or can be considered a viable alternative to current methods for the management and treatment of dental caries. (Cochrane Reviews. Ozone therapy for treatment of dental caries. 2004)

Oxygenation therapists proposed that disease is caused by absence of oxygen and loss of cellular ability to use oxygen for “good energy” metabolism, detoxification, and immune system function. Oxygen therapies are proposed in order to restore the body’s ability to produce “good” energy, to “detoxify” metabolic poisons, and to kill invading organisms. However, over the five decades that have passed since this concept was proposed, scientists have shown that:

  1. Anerobic energy metabolism (fermentation) is not the cause of cancer.
  2. Koch’s glyoxylide does not exist.
  3. Ingestion, infusion, or injection of hydrogen peroxide cannot re-oxygenate the tissues of the body.
  4. Ozone-treated blood infused during autohemotherapy does not kill AIDS virus in vivo. (Green, S. Oxygenation therapy: Unproven treatments for cancer and AIDS. Quackwatch.org)

Ozone therapy has been recommended to treat many conditions. There are numerous anecdotes about successful treatment with ozone therapy, although effectiveness and safety have not been proven scientifically. (Ozone Therapy, Intelihealth article, Natural Standard and Harvard Medical School, 2008)

“Hyperoxygenation” therapy–also called “oxymedicine,” “bio-oxidative therapy,” “oxidative therapy,” and “oxidology”–is a method of cancer management based on the erroneous concept that cancer is caused by oxygen deficiency and can be cured by exposing cancer cells to more oxygen than they can tolerate. The most highly touted “hyperoxygenating” agents are hydrogen peroxide, germanium sesquioxide, and ozone. Although these compounds have been the subject of legitimate research, there is little or no evidence that they are effective for the treatment of any serious disease, and each has demonstrated potential for harm. Therefore, the American Cancer Society recommends that individuals with cancer not seek treatment from individuals promoting any form of hyperoxygenation therapy as an “alternative” to proven medical modalities. (Questionable methods of cancer management: Hydrogen peroxide and other “hyperoxygenation” therapies. CA Cancer Journal for Clinicians. 2008;43(1):47-56.)

There is limited research in veterinary species. A lab animal study of rabbits suggested a benefit for cancer. A couple of recent studies in cows from a single research group in Croatia found a possible benefit of ozone in treating retained placentas and urovagina and in improving reproductive efficiency. An uncontrolled case series in dogs reported improvements in signs of intervertebral disk disease after ozone therapy (though often patients with this disease get better with rest or only supportive care anyway).

As is always the case, there are numerous positive anecdotes claiming dramatic success in treating a wide range of diseases, but for well-established reasons, we cannot rely on these stories as a demonstration that this treatment is safe or effective (c.f. here and here). And there are a few clinical studies suggesting a benefit, all with significant limitations. The balance of the evidence, however, does not support the efficacy of ozone therapy for any condition. Given the miraculous results claimed for this treatment, it would not be difficult at all to generate dramatic clinical trial evidence, so the absence of this evidence, despite decades of use, strongly suggest that the anecdotes and testimonials cannot be trusted.

The underlying theories used to justify the treatment are also dubious. As Dr. Green establishes in his article on Quackwatch, it is not plausible that low oxygen levels are responsible for many of the diseases ozone therapy is supposed to treat, and it is not likely that ozone therapy significantly increases the oxygen available to tissues in a patient that is treated with it. And while the hype about the benefits of antioxidants does not appear justified, it is certainly possible that free radicals and oxidative stress could actually cause health problems in patients treated with a potent oxidizing agent like ozone. Which leads to the question…

Is It Safe?
There are anecdotal reports in the media and in the scientific literature of adverse effects and even death following ozone therapy. Patients have died from gas bubbles in their bloodstream following injectable ozone treatment, and patients have suffered injury from the injection of ozone and from the apparatus used to instill ozone rectally, vaginally, and into body cavities. Accidental infection with HIV and hepatitis virus have also been reported from contamination during autohaemotherapy.

According to one scientific review, “The risks of ozone therapy are played down by its proponents. Yet, numerous reports of serious complications, including hepatitis, and at least five fatalities have been reported.”(Ernst E (2001). A primer of complementary and alternative medicine commonly used by cancer patients. Med J Aust, Jun 4; 174(11): 611-2)

The indirect risk of using ozone therapy, if it is ineffective, is that serious disease can progress and the opportunity to treat with truly effective therapies can be lost if one delays conventional therapy in favor of ozone therapy. The FDA referred to this risk, as well as the more direct hazards mentioned above, when reporting its decision in 2009 to seize equipment used for ozone therapy from a company illegally selling these unapproved medical devices. The FDA considers medical use of ozone as an unapproved drug, which makes such use subject to prosecution.

And as mentioned before, ozone has been intensively investigated as a pollutant, and there are many studies reporting harmful effects in humans and veterinary species.

Bottom Line
The theoretical justifications for the medical use of ozone are weak and unproven. There are equally strong theoretical reasons why such use could be harmful.

Actually clinical research in humans is limited, but there is no consistent body of evidence to suggest ozone therapy is effective for any medical condition. There are anecdotal reports of injury, illness, and death caused by ozone therapy in humans.

The research is even more limited in veterinary species, and there is no consistent body of evidence to support the safety or effectiveness of ozone therapy for disease in dogs and cats.

Medical use of ozone is not approved in the U.S., and there have been prosecutions of individuals selling unapproved medical devices for use in ozone therapy.

Any use of ozone therapy in dogs and cats must be considered experimental and should only be conducted in the context of properly controlled, monitored, and approved clinical research trials. As with all unproven therapies, those selling ozone therapy will claim benefits and deny the risks. But in the absence of reliable information about the effects of ozone treatment, the chances of harming your pet are at least as good as the chances of helping them.

Posted in Miscellaneous CAVM | 41 Comments