Primal Defense-An example of why I am suspicious of probiotics.

Posted on April 19, 2010 by skeptvet

For those who have read what I have previously written about probiotics, you’ll know that I am cautiously optimistic about their potential usefulness as a medical therapy, despite the tendency towards overstating the results of the limited clinical trials so far done in veterinary species. The theoretical principle, that administering living organisms orally can have beneficial effects on the GI tract and, potentially, systemically, is certainly reasonable. And there is clinical evidence supporting benefit in humans for some causes of diarrhea and other GI tract disease. The literature concerning veterinary use is very limited and preliminary, with both possible risks and benefits reported but no clear, indisputable evidence for clinical benefit. Still, I certainly think additional research is warranted, and I do sometimes use some probiotic products in my own patients for antibiotic-associated diarrhea.

However, I have a number of concerns about probiotics. Little is known and less understood about the composition and function of the normal GI flora, and what role, if any, organisms not normally found in the gut can have when given therapeutically is unclear. Independent testing of many probiotic  products has also identified serious quality control problems, so it is currently impossible to trust that what you think you are getting is really in many of the commercial probiotics. However, my biggest concern about probiotics is that their widespread acceptance and use goes well beyond what is justified by the available evidence, and this can easily lead to direct harm and even more easily to the kind of indirect harm that comes from substituting unproven remedies for well-demonstrated ones. Exaggerated claims and unscientific, deceptive marketing practices are common in the promotion of such products, and this raises the chances of their doing more harm than good.  The assumption of safety and efficacy that is often made about CAM products has certainly proven, in the case of some such products, to be unfounded, with real harm resulting.

One of the most egregious examples of this is a product which I recently looked into after hearing a number of my clients talking about using it in their pets. Primal Defense is marketed by Garden of Life, and the marketing materials are a laundry list of exaggerated and unsupported claims. Some examples:

“Healthy people usually have a ratio of approximately 85% good to 15% potentially harmful organisms in the intestinal tract. In some cases, even those who appear to be well might have an unfavorable ratio as a result of daily exposure to environmental toxins and a modern lifestyle. “

Here we have the usual vague “toxin” gambit, suggesting that normal life is full of poisons that we need their product to protect us from.

” Large scale use of pesticides, herbicides and other chemicals has changed the bacterial balance of the soil. In order to obtain the benefits we historically acquired from consuming foods cultivated in healthy soil, Garden of Life developed a Homeostatic Soil Organism Probiotic Blend utilizing 12 species of beneficial microorganisms.” 

The idea that modern agricultural practices can affect soil ecology is pretty obvious. The suggestion that this somehow creates deficiencies in nutrients or human/pet gut ecologies that we need this product to correct is totally manufactured and unsubstantiated in any way.

The very use of the term “Homeostatic” is a bit of pseudoscience marketing, since this term has no recognized meaning with regard to probiotics and was apparently made up just for the purpose of making this product sound “sciency.”

The story, however, gets a lot scarier. The marketing of this product involves a great deal of outright lying and deception. The founder of Garden of Life, Jordan Rubin, was fined by the Federal Trade Commission (FTC) for false advertising in connection with Primal Defense and other product in 2006. This including fabricating claims about clinical research studies to support his product claims. He was also ordered by the Food and Drug Administration (FDA) to desist from making false and unsubstantiated health claims in 2004. Mr. Rubin has also claimed to have several academic credentials, including a NMD (naturopathic medical doctor) and PhD. Both degrees, and other credentials he has claimed, come from unaccredited correspondence schools, one of which was actually ordered to close by the state of Hawaii in 2003 for fraudulent practices.

Marketers of Primal Defense frequently state that there is clinical evidence to support their claims for the product. However, no real clinical trials seem to have been published in any recognized scientific journals. For example, claims are made on a number of websites regarding a clinical trial of Primal Defense supposedly published in the journal Progress in Nutrition (Goldberg, P.A. “Primal Defense Homeostatic Soil Organisms As Applied To Medically Unresponsive Chronic Disease Conditions In Adults” Progress In Nutrition Supplement Volume 4 January 2002). The journal is not listed on PubMed, Science Citation Index Expanded, or any other resources listing legitimate scientific journals. The accusation has been made that it is a fake journal funded by Garden of Life, but I cannot confirm this. In any case, it is clearly not a legitimate peer-reviewed scientific publication, and the author is a chiropractor who seems to publish predominantly in chiropractic journals and newsletters, not real science journals.

A bit more investigation into Mr. Rubin explains pretty clearly his lack of respect for legitimate scientific research or academic credentials. He is the paragon of faith-based medicine whose books, including The Maker’s Diet and Patient Heal Thyself, detail his belief that his own GI disease was cured through a combination of prayer and changes in diet based on “biblical principles.” As he puts it:

“My father had just gotten through telling me he had spoken to an eccentric nutritionist on the phone. My father didn’t want me to get my hopes up so he had investigated the man’s program himself. The nutritionist told my father he believed I was ill because I was not eating the diet of my ancestors, based upon Biblical principles.

When my father told me about all of this, naturally, I was curious…It fit into my belief system. In an effort to start all over, I took myself off all nutritional products and read the Bible to see what people ate thousands of years ago. I also learned that the longest living cultures in the world had one thing in common: they consumed living foods that abounded with beneficial microorganisms.

A few weeks later, I got on a plane, still bound to my wheelchair, and headed for southern California to live closer to the man who would teach me how to eat from the Bible. After integrating into that particular nutritionist’s program some of my own findings about nutrition and health from the Bible I saw some improvement…During my forty days and nights of parking my motor home close to the beach, I prayed, listened to music and planned everything around buying, preparing and eating my food…The combination of the Biblical diet and the HSOs had restored my health.”

The use of science to try and justify Mr. Rubin’s unscientific nutritional theories are pure marketing, taking advantage of the respectability that real science has earned through the results it produces. His approach is ultimately based, as so much CAM is, on personal revelation, and supported primarily through anecdote and testimonial. His books, his Garden of Life company, his Biblical Health Institute, and all the other pieces to his lucrative nutrition business are paradigms of snake oil marketing.  

Such a marketing approach can turn a potentially legitimate, if not yet ready for primetime, therapy like probiotics into pure quackery. If you can’t trust Mr. Rubin’s claims about his own credentials or the research evidence behind his products, why should you have any faith in his products themselves, even if they claim to be something potentially useful like probiotics? CAM marketers like to attack the honesty and ethics of mainstream medical product manufacturers, such as pharmaceutical companies and commercial pet food makers. And all too often, there are real reasons to be skeptical of these industries. But for all that, they have an established, public record of legitimate science behind many of their products, often thanks to vigorous government regulation requiring it. Companies like Garden of Life illustrate why the unregulated supplement industry (aka Big CAM) is not only not entitled to the assumption of better ethics that they often receive, but it quite likely gets away with even more ethically questionable practices than the mainstream medical and diet industries, which are at least better supervised and regulated. I do not often feel justified in prescribing probiotics, but when I do I certainly have no intention of using a product such as Primal Defense marketed by a man who not only bases clearly unscientific advice and products on personal divine revelation but who seems to have no discomfort promoting his ideas and products with obvious and egregious deceit.

Posted in Herbs and Supplements | 94 Comments

Dr. Shawn on Alison Averis’ Essay Fooling Yourself

Posted on April 16, 2010 by skeptvet

The tireless promoter of “natural” veterinary medicine (whatever that is) and himself, Dr. Shawn Messonier, has applied his characteristic fuzzy logic and love of strawmen and misleading hyperbole to a recent guest post by Alison Averis on Fooling yourself: An example of how to fool yourself and how the placebo effect can work in animals. I shall reproduce his post below, with appropriate commentary and clarification (in bracketed, boldface type).

“I recently came across a post on another blog purporting to show that there is no proof that natural/alternative therapies work. [Actually, actually reading Alison’s post will make it clear that this is not the point of it at all. Throughout his essay, Dr. Shawn seems unable to distinguish between an anecdote used appropriately as an illustration and example of a phenomenon, and his preferred use of it as proof of something. Alison’s story was a parable illustrating how easy it is for one’s expectations to color one’s judgment about the efficacy of a therapy not evaluated in an objective, scientific way, not a statement or proof that “natural/alternative” therapies do not work.] This particular blog is devoted to debunking any therapy that falls outside the mainstream. [Actually, this blog is devoted to, as it says at the top of the page, taking a “Science-Based Look at Complementary and Alternative Medicine.” I am happy to validate any non-mainstream therapy that can be demonstrated to be effective in an appropriately scientific way, and I am equally happy to condemn any mainstream therapy that cannot.] The writer of this blog constantly seeks to show that there is no proof that any natural therapy ever works or helps anyone or any pet. [strawman and flagrant demonization]

The post I read was submitted by a reader of this particular blog. Briefly, she shared the following information in her post.
An “alternative therapist” told the owner of a horse that she would “work on” the horse for free if the owner would give her feedback on how the horse performed following the “free therapy session.” Unknown to the owner, the “therapist” never worked on the horse but led the owner to believe she had done so.

The day following the supposed “therapy,” the owner was happy to report that the horse actually “rode better than normal.” The writer of the blog used this one example to prove that natural therapies don’t work and that the reason the owner thought the horse rode better was simply due to the power of suggestion, or the placebo effect. [Again, the example was never purported to prove that “natural therapies,” or even the specific therapy referred to, don’t work. It was intended to illustrate how subjective, uncontrolled observations are an unreliable basis for making a judgment on what works and what doesn’t.]

While this was an interesting post to read, and it can easily deceive people into thinking that this one simple experiment proved that all natural therapies only work by the placebo effect, a more careful examination of the post leaves a lot to be desired.

First, I don’t know what an “alternative therapist” is or what one does. I assume the writer of this blog is referring to some sort of physical therapy such as massage therapy, but that is never explained.

Second, there’s a big difference between someone who claims to be an “alternative therapist” and a licensed doctor trained in integrative medicine. [How, exactly, does one get “licensed” to practice “integrative medicine?” This is a buzzword that simply means the use of unproven therapies alongside scientifically validated ones, and there is no process by which one becomes licensed to do this.]

Third, this particular website on which the blog appears always chastises alternative medicine for the lack of proof for alternative therapies since there are so few well controlled, double-blind placebo-controlled studies. [I have rebutted this charge of relying only on double-blind placebo controlled trials before HERE, yet Dr. Shawn continues to state the falsehood that I rely solely on such evidence.] It’s interesting that this website now uses an example of a poorly designed “study” (if an observation of one patient even constitutes a study) to prove that no natural therapies ever work! [Yet again, the hypocrisy that he gleeful implies is not present, despite his inability to distinguish an example from a proof.]

Fourth, the observation in this case was entirely subjective rather than objective. Rather than using an owner’s observation that the horse “rode better” after a particular therapy, why not use a more objective measurement such as gait analysis or forced plate analysis? In my practice, I can objectively measure things such as a pet’s blood pressure or blood count and easily determine if my therapy (conventional or natural) is working. This can totally eliminate the subjective assessment an owner may make in determining if a pet simply “feels better.” [I would be very interested in how much “objective” measuring of outcomes Dr. Shawn actually does. He seems to imagine he can “eliminate” subjective owner assessments in his practice, but I find this hard to believe. He routinely claims better outcomes for his patients with cancer, for example, than those possible through scientific medicine, yet I am unaware of any formal, scientifically controlled or objective research he has published on the subject, so I wonder how exactly he makes his assessments of his interventions more objective and independent of owner history than the rest of us in clinical practice.]

Fifth and finally, the same “conclusion” could easily be reached in this case if a conventional drug had been used rather than an alternative therapy. For example, suppose a doctor told the same horse owner that he was going to give the horse a pill which would improve its performance. But suppose the doctor secretly did not give the horse the medication but the owner still reported that the horse “rode better” the next day. If we follow the blogger’s (lack of) logic, we have to draw the same conclusion-namely that this one example proves that conventional drug therapy doesn’t work! [No, as I’ve made clear, and as should be obvious from reading the post, the conclusion we would draw would be that the owner report of how the horse performed subsequent to the sham therapy, be it conventional or alternative, is not a reliable assessment of the efficacy of the therapy. The point is that we must have a better level of evidence, and my evaluations of alternative practices such as those advocated by Dr. Shawn is intended to identify whether such evidence is or is not available. He is the one who routinely relies on his personal experiences and intuition and anecdotes as evidence to justify implausible or simply “made up” theories and practices. The whole purpose of this blog is to do better than this sloppy and outdated approach, not to replicate it in favor of or in opposition to any particular therapy.]

It’s interesting how much hatred and negativity one encounters among people who don’t like natural/alternative medicine. [It is also interesting to see how reasoned and civil criticism and a call for real evidence rather than simply opinion is identified as “hatred and negativity.”] To use one example as this blogger has done as universal proof that integrative medicine doesn’t achieve successful results is ludicrous and deceiving. [And, fortunately, not at all what has been done with this example] Fortunately, it’s easy to see through all the hypocrisy in this blog and understand the real goal of people who write this rubbish-destroy your choice in determining what kind of therapy you would like for you, your family members, and your pets. [Wow, “rubbish.” There’s a polite and thoughtful critique for you. As for the question of choice, I’ve addressed this bit of misdirection before. Offering as alternatives treatments which have not been demonstrated to be safe or effective, or which have actually been clearly demonstrated not to be so, is not offering choice–it is offering false hope at best and lies at worst, and these are not what our patients or clients deserve from us.]”

Posted in General | 4 Comments

The Mysterious Vanishing Placebo Effect?

Posted on April 11, 2010 by skeptvet

I have written about the placebo effect before, but a recent update to a Cochrane review entitled Placebo Interventions for All Conditions has prompted me to revisit the subject. It has been clear for some time that the so-called placebo effect is not an example of the power of the mind to overcome disease. There is no evidence that therapies which have no measurable biological affect can truly alter the progression or outcome of an illness. No matter how you feel when given a deliberate placebo or an inert CAM therapy, you don’t live longer, your tumor doesn’t get smaller, you blood sugar doesn’t become normal, and the objective effects of your disease on your body don’t change.

What has seemed reasonable to me in the past is the idea that there might be real benefits in terms of subjective symptoms, such as pain or nausea, attributable to placebo effects. However, I am a little less confident of that in light of this recent review.

The review was a metanalysis of clinical trials which included both placebo and no treatment groups. As expected, no significant clinical effects were found for any objectively measurable variable. However, even in the case of subjective variables like pain and nausea, the best the authors could say was, “in certain settings placebo interventions can influence patient-reported outcomes, especially pain and nausea, though it is difficult to distinguish patient-reported effects of placebo from biased reporting.”

For pain, some trials reported little or no effect, and those that reported a large effect were all conducted by the same group of researchers, which raises suspicions about the reliability of the findings. Findings for most other subjective measures either showed no benefit from placebo, or effects that varied enormously from one study to another, suggesting differences in the studies were responsible for differences in the findings. If the placebo effect were a consistent, reliable phenomenon one would expect it to show up about the same regardless of who is studying it.

The metanalysis also found that how much benefit patients seemed to get from placebo treatments depended heavily on whether they thought they might be getting a placebo treatment. Inert treatments worked better in trials where the subjects were told that no placebo would be given.

These findings and others like them make it seem very likely that the placebo effect is less a feature of the human mind than it is an artifact of  clinical trial design, a conglomeration of biases and measurement errors rather than mind over matter. The better one controls for biased reporting of effects, the less effect one sees. This is not how the results look when one studies an unequivocally effective therapy, even one involving subjective symptoms, such as NSAIDs for arthritis pain. Effects from real therapies are consistently seen in different studies by different researchers, and they do not disappear when the trials become better controlled for bias.

Of course, if someone tells you they have pain or nausea, and then you give them a placebo and they say they have less pain or nausea, can you really say the effect isn’t real? If these phenomena are ultimately subjective, than regardless of the biological events underlying them the perceptions of the sufferer must be the critical determinant of benefit. Still, most of the research on placebos and sham therapies suggests that when well-designed studies are conducted, these benefits are small and do not reach anything like the level of clinical significance of true therapies for these symptoms. And, as I have discussed before, taking advantage of what benefit may occur due to placebo effects requires successfully deceiving the patient, which raises significant ethical concerns.  The lesson of this review seems to be that placebo effects may turn out to be mostly illusory, artifacts of inadequate study design, and we should be hesitant to rely on them for treatment of any clinically significant symptoms.

Posted in General | 2 Comments

What Scientists Say and What the Public Hears

Posted on April 8, 2010 by skeptvet

There are many barriers to public understanding of science and scientific research, ranging from low levels of science literacy in the general population to frequently  poor communication skills among scientists. I recently ran across a pithy summary of some common technical jargon used, in this example, in discussing vaccine safety, and the corresponding interpretation non-scientists are likely to give these terms. I have adapted it slightly from the source, an excellent book on the question of vaccine safety titled Do Vaccines Cause That?! A Guide for Evaluating Vaccine Safety Concerns by Martin G Meyers and Diego Pineda. Many of these kinds of confusion come up a lot when I am discussing the scientific evaluation of medical therapies with non-scientists, and they are a perennial source of confusion and frustration for all concerned. I’m sure you can all think of many others, so feel free to add as many as you can to the list and I will eventually try to compile something more comprehensive.

Expression/Word What Scientists Mean What the Public Hears
Adverse event Something that occurs at the same time as a medical intervention, which may or may not be related Something bad caused by the intervention
Bias Systematic error that could lead to mistaken conclusion. Not having an open mind
Favors rejection of the hypothesis The data suggest the hypothesis isn’t true, but you can never wholly prove a negative We still don’t know
The findings won’t go away We couldn’t find an alternative explanation We’re trying to fudge the data
Inadequate to accept or reject the hypothesis The data do not allow a definitive statement We don’t know
Naïve Not previously exposed to X Unsophisticated, stupid
Plausible Theoretically possible Likely, probably true
Relative risk The difference in risk between two groups or populations or conditions in an experiment The risk
Safe Insignificant risk No risk
Significant Not due to chance Important, real
Not significant Due to chance Unimportant
No evidence for X No definitive conclusion about X is possible X may be true we just can’t prove
No evidence against X No  definitive conclusion about X is possible X probably is true
Posted in General | 10 Comments

The Dunning-Kruger Effect: Why incompetence is blind to itself.

Posted on April 6, 2010 by skeptvet

“The trouble with the world is that the stupid are cocksure and the intelligent are full of doubt.”
Bertrand Russell

“Ignorance more frequently begets confidence than does knowledge.”
Charles Darwin

“It is one of the essential features of such incompetence that the person so afflicted is incapable of knowing that he is incompetent.”
William Ian Miller

I recently stumbled across an article on the Dunning-Kruger Effect, a theory of psychology that claims, “…the skills that engender competence in a particular domain are often the very same skills necessary to evaluate competence in that domain-one’s own or anyone else’s…” What this means in ordinary terms, is that while we all overestimate our own knowledge and skills, the less competent we are at something the more will will overestimate our abilities.

The original article is Unskilled and unaware of it: How difficulties in Recognizing one’s own incompetence lead to inflated self-assessment, and it is well worth a read. The authors conducted a number of experiments on that paradigm of Guinea pigs, the undergraduate psychology student. They gave them tests of social skills (recognizing how funny jokes were compared to a standard of professional comedians’ assessment) and cognitive skills (English grammar and logical reasoning), and they evaluated the accuracy of the subjects’ self-assessment compared with their actual performance. Those in the bottom quartile were most likely to overestimate their skills by the largest amount.

Subsequent tests and analyses indicated that this inaccurate self-assessment was tied to the lack of the same skills needed to perform well on the tests. Those subjects in the top quartile consistently underestimated their performance, but when exposed to representative samples of other subjects’ tests, these top performers were able to adjust their self-assessment appropriately, whereas the bottom quartile subjects did not correct their inaccurate self-assessment based on being able to see directly how their peers performed.

How is this relevant to medicine? Well, in the obvious way that the very people who most need to improve their knowledge and skills and those who are least likely to be able to see that they need this improvement. We all rationalize our failures under the pressure of cognitive dissonance, and we all assess ourselves more charitably than we assess others. But the Dunning-Kruger Effect suggests that those of us with the weakest skills, whether it be in medicine specifically or in the kinds of critical thinking necessary to separate truth from nonsense, we are also the least likely to be able to recognize our own deficiencies.

There is some good news, however. The study also looked at whether or not the least competent subjects could improve the accuracy of their self-assessment. As it turns out, if you make them more competent, by training them on the skills they are being tested on, they also become better able to accurately gauge their own performance. That’s a strong argument for widespread teaching of critical thinking skills and the skeptical outlook, since it suggests we can do better in both our assessments of the world around us and our judgments of our own capabilities.

Posted in General | 8 Comments

Simon Singh Wins a Victory in BCA Libel Suit

Posted on April 1, 2010 by skeptvet

As many of you may know, there is a libel cases in Britain that has been followed very closely by those of us supportive of evidence-based medicine, that of Simon Singh versus the British Chiropractic Association (BCA). Dr. Singh is a science journalist and author, and with Edzard Ernst he wrote Trick or Treatment: The Undeniable Facts about Alternative Medicine, which I have previously reviewed. The lawsuit stems from an article Dr. Singh wrote in the Guardian newspaper criticizing the BCA for promoting chiropractic treatment for clearly inappropriate conditions despite clear evidence against doing so. In the article, Dr. Singh says:

“The British Chiropractic Association claims that their members can help treat children with colic, sleeping and feeding problems, frequent ear infections, asthma and prolonged crying, even though there is not a jot of evidence. This organization is the respectable face of the chiropractic profession and yet it happily promotes bogus treatments.”

The BCA alleges that “happily promotes bogus treatments” implies deliberate fraud or deception, despite the fact that Dr. Singh has clearly stated his opinion that the organization and its members quite likely believe in the bogus therapy they practice. In Britain, libel law places the burden of proof on the defendant, and it can be very difficult to prove that one did not mean what the plaintiff alleges one meant. This practice makes scientists and others who criticize CAM practices on the basis of sound evidence against them vulnerable to expensive and demoralizing lawsuits intended to intimidate them, and the media which might otherwise publish their critique.

Initially, Dr. Singh faced a significant setback in the lawsuit when a judge ruled his comments were factual assertions, not expressions of opinion, which meant that unless he could prove to a high degree of certainty that the BCA intentionally promoted therapies it knew were ineffective, he would be guilty of libel. An appeals court has now reversed that ruling, declaring Dr. Singh’s statements as opinions, which carries a much lower burden of proof for defending against libel claims.

What is encouraging about this ruling is the language of the opinion, which suggests the higher court recognizes that libel laws are structured in a way to make them easy to abuse in attempts to intimidate legitimate critics of unfounded medical practices. The justice wrote:

“The opinion [expressed in an article like Singh’s] may be mistaken, but to allow the party which has been denounced on the basis of it to compel its author to prove in court what he has asserted by way of argument is to invite the court to become an Orwellian ministry of truth…[those claiming they had been libelled] cannot, by simply filing suit and crying ‘character assassination!’, silence those who hold divergent views, no matter how adverse those views may be to plaintiffs’ interests.

Scientific controversies must be settled by the methods of science rather than by the methods of litigation. More papers, more discussion, better data, and more satisfactory models – not larger awards of damages – mark the path towards superior understanding of the world around us.”

Of course, the court has no authority to alter the law. However, there is an active movement in Britain to reform libel laws so as to allow open scientific debate and the kind of vigorous criticism based on logic and evidence needed to ensure good ideas in medicine prosper and bad ideas are cast aside. It is shameful that Dr. Singh has spent £200,000 and two years of his life battling this clear attempt at intimidation, and his battle is not yet over. But perhaps his case will be the stone that starts an avalanche of real libel reform.

Posted in Chiropractic, Law, Regulation, and Politics | 5 Comments

Micronutrients and Cancer

Posted on March 29, 2010 by skeptvet

A recent editorial in the Journal of the National Cancer Institute (JNCI) addresses the issue of whether micronutrients, such as vitamins, have a clear role in cancer prevention. It is fairly common in broad  epidemiological survey studies to look for associations between levels of risk of a particular disease and lifestyle variables. Casting such a broad net often snags a number of associations, some of which may later prove causal and important, many of which will turn out to be spurious or at least complex and not direct cases of the lifestyle variable being responsible for the greater or lesser risk of the disease observed.

The vitamin content of the diet is a common variable found to be associated with lower risk of some diseases, including cancer, and this tends to suggest that vitamin supplementation may be protective. However, the logic behind that assumption is quite shaky. For one thing, there is a huge difference between eating foods rich in folate or Vitamin C or omega 3 fatty acids or whatever, and taking these as supplements. Foods are complex mixture of nutrient and non-nutrient substances, and while in some cases individual nutrients are clearly critically important for health (such as Vitamin C for preventing scurvy), many times the overall pattern of the diet may be more important than any individual component.

But because of the historical success of vitamin supplementation eliminating a few common diseases that were due to vitamin deficiencies, we tend to have a warm and fuzzy feeling about vitamins. And, of course, in America if some is good more is always better! Except when it isn’t.

The editorial in JNCI points to many studies in which vitamin supplementation proved to be useless for cancer prevention, and even a few in which vitamin supplementation appeared to increase cancer risk. For example, beta carotene and Vitamin E have been shown to increase the rate of lung cancer, and overall mortality, in smokers. Diets high in folic acid have been associate with a lower rate of colorectal cancers, but some experimental trials on folic acid supplementation shown no benefit and even suggest they may increase the rate of this disease, and also prostate cancer.

Such research evidence reminds us that as much as we desires simple stories, and clear good guys and bad guys, health and disease are complex. Vitamins can be beneficial, useless, or harmful like any other potential preventative or treatment, and we must rely on solid evidence rather than assume the benefit or safety of such substances, whether “natural” or not.

Posted in Nutrition | Leave a comment

Nice Post on Equine CAM by Alison Averis

Posted on March 26, 2010 by skeptvet

Being a small animal  vet, I don’t have much first-hand experience with equine CAM. But our recent guest blogger, Alison Averis, is very involved in equine issues, and she has a nice article in the Equine Independant on judging alternative claims in this area. She is also dealing with the usual sorts of critiques that defend CAM and challenge science-based medicine without ever resorting to facts or evidence but trying to find fallacious rhetorical strategies to undermine arguments without addressing them. She’s holding her own just fine, but it wouldn’t hurt to offer her some support if you can, particularly those of you more familiar with horse medicine.

Posted in Guest Posts, Miscellaneous CAVM | 3 Comments

More Natural Nonsense and Unethical CAM Marketing

Posted on March 25, 2010 by skeptvet

A colleague recently saw an older dog who had vomited up roundworms and was doing some coughing. He diagnosed and treated the patient appropriately, but the client later contacted him with questions about some alternative remedies that had been recommended to her by the folks at Native Remedies. The owner had the common misconception that “natural” is a word with a real and precise meaning in medicine (as opposed to a marketing term invented to take advantage of the fear of “toxic” modern life) and that using it to describe a remedy somehow guaranteed safety. The folks trying to sell her such products took full advantage of this idea in their letter to her.

They began by flattering her, “You are to be commended for researching the use of natural alternatives.” They then recommended a host of herbal and homeopathic products.

Several were claimed to be homeopathic products: Respo-K, Sinu-Rite, and KC-Defense. These contain a variety of ingredients all diluted in the usual homeopathic way. 100% safe? You bet! Why–because they’re 100% water! (Well, technically some of the ingredients are diluted less then 12C, so they could possibly contain a few molecules of the original substance, but still quite likely much less than needed to have any measurable physiologic effect). The seller did engage in a bit of deceptive advertising. They repeatedly stressed the products are “FDA registered.” Well, doesn’t this mean they are tested and approved by the FDA?

Actually, not at all. The issue of how homeopathic preparations are regulated is a complex, and fuzzy one. Homeopathic products for human use were grandfathered, without any scientific testing or validation, into the original legislation establishing the FDA and its mandate as a concession to an influential senator who was a homeopath. These products can be marketed with medical claims as long as they have been included in the Homeopathic Pharmacopeia of the Untied States, an index of such remedies maintained by an independent organization of homeopaths which sets rigorous standards for proving the safety and efficacy of water in a way totally inconsistent with the rest of medical science. The over-the-counter sale of such remedies is limited to disease that are “self-limiting” and which an average consumer should be expected to recognize and be able to treat on their own. If the homeopathic “drugs” are used for serious illnesses, they require a prescription, though for obvious reasons they seldom are so used.

With regard to the veterinary use of homeopathic “drugs,” the FDA has stated that it does not considered this activity to be covered under the same rules as the human use of these products, so veterinary homeopathy is technically a use of unapproved veterinary drugs and so illegal, though doubtless lawyers could wade through the voluminous legislation and make all sorts of arguments for and against this claim. In any case, the FDA has neither the will nor the resources to enforce any such position and has generally agreed to ignore homeopathy when used in companion animals.

All of this is simply to illustrate that “FDA registered” when applied to a homeopathic drug 1) implies no scientific testing of safety and efficacy and 2) only properly applies to human use, which was allowed in the 1930s as a political concession. Thus, the term is meaningless from the point of view of legitimizing any claims sellers of these products may make.

Because these remedies are essentially only water, and so harmless in themselves, there is not likely ever to be any interest among politicians in the controversial and thankless task of requiring them to either prove themselves scientifically or be banned. But it is clear that they should not be expected to have any benefit for real disease, nor should they be used in place of scientific medicine which has demonstrated safety and efficacy in a legitimate way.

The other two recommended products were herbal concoctions, and so have some potential to be helpful or harmful. The usual caveats apply to these remedies, namely that they are in no way regulated and all quality control is voluntary, so cases in which the label does not accurately reflect the ingredients and toxic or pharmaceutical contaminates are present are common. I have a long, and growing, list of examples of this problem.

The first nostrum reocmmended was Parasite Dr., which the sellers claim is a mixture of wormwood (Atremesia absinthinium), Cloves (Eugenia caryophyllata), Neem (Azadirachta indica), and Herb of Grace (Ruta graveolens).

Wormwood has been used medicinally and as a flavoring agent for centuries, most notoriously in the alcoholic drink absinthe. Limited in vitro studies have shown some toxicity to roundworms, however, these must always be interpreted cautiously since bleach can poison worms in a test tube too, but that doesn’t make it a safe and effective deworming agent. There is one in vivo trial in sheep conducted in India in which water and alcohol extracts of the plant had some effects on parasite egg counts, but again when one takes extracts from a plant and purifies them, one has a drug, not an herbal remedy. How much of which compounds from wormwood are in this product is completely unknown, so even if wormwood had antiparasitic properties, which is far from demonstrated, that doesn’t mean this product would. As for toxicity, one small rat study found no obvious toxic effects, however neurologic and GI symptoms have been reported from ingestion of compounds in wormwood, so the safety of this product is as much a mystery as its efficacy. No evidence concerning safety or effectiveness in dogs appears to exist.

Clove oil has also had a history of medicinal and flavoring use. The NCCAM has concluded there is insufficient evidence to support any use other than as a mild topical analgesic, and a review of traditional veterinary herbal remedies for GI and parasite problems has concluded there is insufficient evidence to justify its veterinary use. There have also been reports of an increased risk of bleeding, particularly when used concurrently with non-steroidal anti-inflammatory medications, and allergic reactions have been seen. No evidence concerning safety or efficacy in dogs specifically appears to exist.

Neem is currently quite popular among gardeners as an insect repellant, and has a history of use as an anti-parasitic. There is reasonable evidence for its topical use on animals and plants, including one study showing some flea repellent effects in dogs and cats. Extracts have been tested in several trials in sheep, and most have found little or no efficacy in reducing intestinal parasites. (1, 2, 3, 4). A review of the limited safety data available for humans and lab animals finds minimal toxicity, and the EPA has exempted some neem products from its more stringent pesticide regulations under the presumption of safety. However, no data on the safety or oral use in dogs appears to exist.

Finally Rue or Herb of Grace is primarily known in traditional herbal use as a substance used to induce abortion. There is limited data on it’s safety and efficacy, and nothing to support its use for parasites or gastrointestinal disease generally. Some pretty serious toxicity, including photosensitivity (blisters and ulcers developing with sun exposure after use of rue) and potential mutagenic and carcinogenic properties have been reported.

So the pattern is clear. Minimal or no evidence of effectiveness, limited evidence of safety or even known risks, and no assurance of any particular ingredient or dose or the absence of toxic contaminants. Yet we are supposed to rest comfortably in the confidence that because it’s “natural” it must be good regardless of whether there is any evidence either way.

The folks at Native Remedies are very tricky in their marketing of this and the other products recommended. When one searches their web site for Parasite Dr, for example, the search turns up a clear (and illegal) medical claim: 

1.

Parasite Dr. – Naturally treats canine and feline parasites, hookworm, heart worm, roundworm.
… and Roundworms. Parasite Dr.™ is a …
… canine and feline parasites, hookworm, heart …

However, when one follows the link to the actual page, they are very careful only to make allowable “structure and function” claims, such as these:

Parasite Dr. Benefits:

  • Promote digestive health and balance
    Calm and soothe the digestive system
  • Cleanse and detox the digestive system and improve digestive functioning
  • Cleanse the blood
  • Support correct balance of intestinal flora
  • Act as a tonic for the entire digestive system
  • Support the immune system

They even go so far as to note, “ Disclaimer: Testimonials have been edited to comply with FDA regulations. While positive results are likely, the testimonials used are general results and are not intended to represent or guarantee that anyone will achieve the same or similar results – individual results may vary.”

Unfortunately, this is merely an effort to comply with the letter of the law, and they show no restraint in making illegal and unethical claims in their e-mail to the client. The nostrum is promised to “rid your pet of unhealthy infestations of internal parrasites without the unwanted side effects sometimes associated with synthetic parasite medication…As an added bonus, Parasite Dr . also helps to cleanse the system and contains herbs with antifungal properties, thus helping to reduce systemic yeast infections which compromise health…” Clearly, the evidence supports none of these claims, and the old saw about “yeast infections” as a cause of illness is a bit of popular CAM mythology which has nothing to do with this patient’s problem.

The most disturbing and ethically offensive part of the marketing materials, however, concerns heartworm disease. This is a serious parasitic infection which is widespread in much of the United States and which is routinely fatal if acquired. There are, however, safe and effective, FDA approved and adequately tested, preventatives in common use. The native Remedies representative, however, claims their product is an effective preventative for this deadly disease, which it almost certainly is not. They also imply conventional preventatives “can undermine the liver” (which is not at all true, while they have risks like any drugs, these have nothing to do with the liver), and they then try to sell another herbal concoction, Detox Plus, to treat this. Any owner unfortunate enough to believe these lies and who lives in an area where heartworm disease is endemic is likely to see their pet die from heartworm infection if they follow this advice. That is why such claims are illegal, not some sinister conspiracy of government and the pharmaceutical industry to deny people effective natural medicines. It is only a pit that the government has not the will or resources to enforce such laws, and that pets and people must inevitably suffer for it.

Posted in General, Miscellaneous CAVM | 8 Comments

Yunnan Paiyao–Secret Herbal Formula to Stop Bleeding?

Posted on March 17, 2010 by skeptvet

Call it coincidence, confirmation bias, or a trend, but I once again ran into the issue of a specialist I refer to recommending a questionable therapy for one of my patients. I recently diagnosed a dog with a nasal cancer and sent him to a board-certified oncologist to consult of options for advanced therapy. The particular disease can’t be cured, but radiation and chemotherapy can have some symptomatic benefit and may prolong a reasonable quality of life. The owner, however, didn’t feel the possible benefits justified the risks and costs, which I think was a reasonable decision. So the oncologist was only able to offer minimal symptomatic care. He offered a non-steroidal anti-inflammatory for pain, and also told the owner to go to a human herbal remedy shop and find the Chinese herbal preparation yunnan paiyao to help with the intermittent nosebleeds the cancer was causing.

I expect specialists to be more cognizant of the need for evidence-based practice than general practitioners, but I am beginning to doubt the truth of this assumption. I accept that sometimes, when there is a compelling need to treat and no established effective treatment available or acceptable to the owner, it may be appropriate to try things that have a weak basis in basic or clinical evidence. However, I am still concerned about the wisdom of recommending therapies that we don’t have at least some reasonable evidence are safe or effective.

Absence of evidence is not, of course, proof something doesn’t work. But it is absence of any good reason to think it does. And the reverse is true for safety. Absence of evidence of harm does not mean it isn’t harmful, only that we don’t know whether it is or not. Yet anecdotal experience is used to justify both safety and efficacy despite the clear evidence of history that this isn’t reliable. Of course, this logic is preferentially applied to CAM therapies. If clinical testing of a pharmaceutical company medicine finds no significant side effects, and then rare harm does appear once the drug is in widespread use, this is trumpeted as a failure of the whole scientific testing paradigm and proof of the evil venality of drug companies and the innately poisonous nature of their products. Yet we seem very comfortable prescribing herbal products about which almost nothing is known concerning safety or efficacy, with the assumption that they must be safe and that even if the only evidence they work is anecdotal at least we they can’t do any harm.

So what is yunnan paiyao, and what is the evidence for or against it? It is an herbal concoction apparently invented in China in the early 20th century, and the details of the ingredients are still kept secret. However, it is widely considered to consist primarily of Panax notoginseng of pseudoginseng root, with a number of other possible plant ingredients. Right away I wonder at the wisdom of prescribing a remedy when no one knows exactly what is in it. Can you imagine a major pharmaceutical company getting away with selling a drug that doctors actually prescribed without disclosing the actual ingredients?! And given the well-documented problem of heavy metal and pharmaceutical contamination of Chinese herbal remedies, and the general inconsistency of such preparations, it is remarkable that any doctor, much less a boarded specialist, would feel comfortable assuming the safety of such a product based on personal experience and anecdotes.

There have been a few papers published in China and in some alternative medicine publications that show the substance has some influence on platelet aggregation, an important step in blood clotting. However, you can mix sand or many other substances in a test tube with platelets and they will activate. One of the reasons it is so hard to make a safe artificial heart is that it’s tough to find substances that don’t trigger platelet aggregation. Some studies have compared the effect of yunnan paiyao with wheat flour or other substances to show it is more likely to cause clotting than these others, but the reliability of the tests and the choice of substances doesn’t make a very convincing case. And we have to remember the problem with the reliability of different sources of published research. Publication bias (the publishing of only positive results and “round-filing” of negative studies) is a problem everywhere. But Chinese journals almost never publish negative studies, and CAM journals are especially prone to select only those papers for publication that support the kinds of therapies the journals were started to promote.

The same issue arises in considering the few clinical trials in humans. A small number of trials with a small number of patients conducted and/or published in low reliability sources might be enough to justify further research, but not to justify widespread clinical use of the product. And, of course, the testimonials and anecdotes of clinicians and users have the same lack of reliability. If the product has been in use for over 100 years, and in that time we have only a handful of small studies of it, I think that is fair reason to be skeptical. If the drug truly has a dramatic impact on bleeding, topically or orally, it shouldn’t be difficult to conduct and publish a well-designed trial for a mainstream journal. Even one such trial would doubtless excite enough interest, through NCCAM or private industry, to stimulate more. Whether this has never been done because the proponents of such therapies don’t see the need for such evidence, or because the drug doesn’t truly have enough promise to survive such a test, is an open question.

Finally, I have found only two published veterinary trials investigating yunnan paiyao. An abstract presented at the 2002 International Veterinary Emergency and Critical Care Symposium took a group of 6 healthy ponies, and anesthetized them twice to check activated clotting time (ACT) and template bleeding time (TBT). The ACT is a moderately reliable test of blood clotting, though it can be affected by temperature, how vigorously and consistently the test tube is shaken, and a number of other factors. The TBT is a much less reliable and more subjective test in which a lancet is used to cut the patient (usually on the oral mucosa) and the time it takes for the cut to stop bleeding is measured.

The only difference reported in methods between the control trial and the yunnan paiyao trial was the position of the patients. They were on their side in the control trial and on their back in the test trial. I wonder if this might affect TBT since the  blood flow to different parts of the body is affected by body position, but there isn’t any information in the abstract to determine if this is a factor. The study reported no difference in the ACT value with or without the yunnan paiyao but did report a non-chance difference in the TBT.

The other trial was a placebo-controlled trial of yunnan paiyao and another herbal preparation called Single Immortal using five Thoroughbred horses. The horses were run on a treadmill after having received either one of the herbal preparations or the placebo (cornstarch) orally twice a day for 3 days before the experiment. A number of variables were measured, with the main goal to see if there was any effect on exercised-induced pulmonary hemorrhage (EIPH), bleeding in the lungs during exercise. No effect of either remedy on EIPH was seen.

So we have a treatment with uncertain and unregulated ingredients, no demonstrated plausible mechanism of action, a few in vitro and lab animal studies in journals of questionable reliability, a few small human clinical trials in similarly questionable sources, and two very small veterinary trials in equids which found no effect except possibly on a poorly reliable and subjective test of blood clotting. At the same time, we have almost no published reports of adverse effects. There is one case report in a Chinese journal of a contact dermatitis reaction and some suggestion that high doses or chronic use may affect bone marrow cells. And we have a well-established history of toxic contamination and poor quality control in Chinese herbal remedies in general.

For me, this information clearly shows the oncologist’s use of this preparation in my patient to me essentially an uncontrolled experiment with no reasonable assurance of safety or efficacy. It is disturbing to me and certainly shakes my confidence in the judgment and recommendations of this particular specialist, though I fear he may not be at all exceptional but simply part of a larger phenomenon in which anecdote, personal experience, and “expert” opinion is given undue weight and the need for more reliable evidence is underestimated in veterinary medicine.

References:

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

Graham L. Yunnan Paiyao–Where’s the clinical evidence? Veterinary Botanical Medicine Association Symposium Archive 2005. Available at: http://www.vin.com/Members/proceedings/Proceedings.plx?CID=VBMA&PID=13730&Print=1&O=VIN

Graham L, Farnsworth K, Cary J. The effect of yunnan baiyao on the template bleeding time and activated clotting time in healthy halothane anesthetized ponies. Proceedings International Veterinary Emergency and Critical Care Symposium 2002, San Antonio, TX. Journal of Veterinary Emergency and Critical Care 2002;12(4):279. Abstract only.

Robinson N. Yunnan Paiyao; The following references come from Dr. Robinson’s document:

1 Bergner P. Panax notoginseng Yunnan bai yao): A must for the first aid kit. Medical Herbalism. 10-31-94 6(3):12.

2 Fratkin J. Chinese Herbal Patent Formulas – A Practical Guide. Santa Fe: Shya Publications, 1986. P. 133.

3 Fratkin J. Chinese Herbal Patent Formulas – A Practical Guide. Santa Fe: Shya Publications, 1986. P. 133.

4 Zheng YN et al. Comparative analysis of the anti-haemorrhagic principle in ginseng plants. Acta Agriculturae Universitatis Jilinesis. 1989;11(1):24-27, 102. [Article in Chinese].

5 Jin H, Cui XM, Zhu Y, et al. Effects of meteorological conditions on the quality of radix Notoginseng. Southwest China Journal of Agricultural Sciences. 2005;18(6):825-828.

6 Fan C, Song J, and White CM. A comparison of the hemostatic effects of notoginseng and Yun Nan Bai Yao to placebo control. Journal of Herbal Pharmacotherapy. 2005;5(2):1-5.

7 Fratkin J. Chinese Herbal Patent Formulas – A Practical Guide. Santa Fe: Shya Publications, 1986. P. 133.

8 Liu Y, Xie M-X, Kang J, et al. Studies on the interaction of total saponins of panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy. Spectrochimica Acta. Part A. 2003;59:2747-2758.

9 Chan RYK, Chen W-F, Dong A, et al. Estrogen-like activity of ginsenoside Rg1 derived from Panax notoginseng. Journal of Clinical Endocrinology and Metabolism. 2002;87(8):3691-3695.

10 Cicero AFG, Vitale G, Savino G, et al. Panax notoginseng (Burk.) effects on fibrinogen and lipid plasma level in rats fed on a high-fat diet. Phytotherapy Reearch. 2003;17:174-178.

11 Epp TS, McDonough P, Padilla DJ, et al. The effect of herbal supplementation on the severity of exercise-induced pulmonary haemorrhage. Equine and Comparative Exercise Physiology. 2004;2(1):17-25.

12 Chung VQ, Tattersall M, and Cheung HTA. Interactions of a herbal combination that inhibits growth of prostate cancer cells. Cancer Chemotherapy and Pharmcology. 2004;53:384-390.

13 Chen FD, Wu MC, Wang HE, et al. Sensitization of a tumor, but not normal tissue, to the cytotoxic effect of ionizing radiation using Panax notoginseng extract. American Journal of Chinese Medicine. 2001;29(3/4): 517-524.

14 Chen FD, Wu MC, Wang HE, et al. Sensitization of a tumor, but not normal tissue, to the cytotoxic effect of ionizing radiation using Panax notoginseng extract. American Journal of Chinese Medicine. 2001;29(3/4): 517-524.

15 Leung KS-Y, Chan K, Chan C-L, et al. Systematic evaluation of organochlorine pesticide residues in Chinese materia medica. Phytotherapy Research. 2005;19:514-518.

16 Leung KS-Y, Chan K, Chan C-L, et al. Systematic evaluation of organochlorine pesticide residues in Chinese materia medica. Phytotherapy Research. 2005;19:514-518.

17 Leung KS-Y, Chan K, Chan C-L, et al. Systematic evaluation of organochlorine pesticide residues in Chinese materia medica. Phytotherapy Research. 2005;19:514-518.

18 Leung KS-Y, Chan K, Chan C-L, et al. Systematic evaluation of organochlorine pesticide residues in Chinese materia medica. Phytotherapy Research. 2005;19:514-518

Posted in Herbs and Supplements | 78 Comments