Denamarin: Does it prevent chemotherapy-induced liver damage?

Posted on August 8, 2011 by skeptvet

Silymarin and s-adensylmethionine (SAM-e) are plant-derived chemicals frequently used as supplements for a wide variety of applications. I’ve written about both before, evaluating the available evidence in humans and in dogs and cats (1,2,3). So far, the evidence concerning the safety and efficacy of these supplements is limited and conflicting. A recent study, however, provides a little bit more low-level support for the use of at least one combination product, known as Denamarin, containing these chemicals.

KA, Hammond GM, Irish AM, Kent MS, Guerrero TA, Rodriguez CO, Griffin DW. Prospective Randomized Clinical Trial Assessing the Efficacy of Denamarin for Prevention of CCNU-Induced Hepatopathy in Tumor-Bearing Dogs. J Vet Intern Med. 2011 Jul;25(4):838-45.

In this study, fifty dogs being treated for various cancers with the chemotherapy agent lomustine (CCNU) were randomly divided into two groups. One group was given Denamarin and the other was not. CCNU is known to frequently cause increases in liver enzymes measured in the blood. Although it is much more rarely the cause of serious liver damage, the elevations in liver enzyme levels often causes concern that can lead to delaying or discontinuing use of the drug. The goal of the study was to see if Denamrin could prevent the increase in liver enzyme levels.

In terms of this narrow criteria, the study showed a positive effect. While only 68% of the dogs on Denamarin showed liver enzyme increased, 86% of those not on the supplement had increased levels of the major enzyme of interest, alanine aminotransferase (ALT). And while these elevations reached the highest levels in 28% of the control dogs, only 7% of the dogs on Denamrin showed such very high increases in ALT.

There are a number of caveats, however, that limit the degree to which these results can support a general recommendation to use Denamarin in dogs given CCNU. The cause of liver enzyme elevations was not determined in most dogs, so it is possible that a progression of the underlying cancer, rather than the CCNU, caused the increases in some of these dogs. And only 1 of the fifty dogs actually showed clinical symptoms associated with liver damage, so it even if Denamarin prevents increased enzyme levels, this may or may not have any actual clinical benefits.

Methodologically, there are some additional caveats that must be considered in judging the significance of this study. There was no placebo group, and owners and investigators were not blinded to the treatment group. While this potential source of bias would not have directly affected ALT measurements, it could potentially have led to differences in how the dogs in the two groups were treated, which might have indirectly affected these levels. This is especially a concern since the study was funded by the manufacturer of Denamarin, and several of the authors have financial links to the company.

Overall, this study provides low-level evidence that Denamarin may have benefits in protecting against CCNU-induced liver damage in dogs with cancer. Independent replication with better controls and more comprehensive assessment of outcome would help to determine if the current results truly represent a clinically meaningful benefit from this supplement or not. However, given the low level of risk associated with this specific product, it is not unreasonable to consider using this supplement for this indication. This does not, of course, translate into support for a generalized use of Denamarin for any and all liver problems.

 

 

Posted in Herbs and Supplements | 16 Comments

Neoplasene: Benefits Unproven and Risks Severe

Posted on July 27, 2011 by skeptvet

Two years ago, I wrote about an herbal product called Neoplasene, an excharotic derived from bloodroot that is marketed for treatment of cancer. I pointed out in that article that apart from a couple of in vitro studies suggesting the active chemical ingredient has some interesting effects on cancer cells, there is little evidence the product is an effective cancer treatment. And there is ample anecdotal and in vitro evidence of harm caused by the product, which kills healthy tissues as well as cancer cells and has been shown in humans to create horrible wounds while leaving hidden cancer that later spreads and kills the patient. No controlled research has been done in dogs and cats, and there is no reliable evidence to support the claims made by the marketers of this product.

Nevertheless, due to the power of anecdotes, and the weakness of government regulation of herbal products, this preparation is still marketed for use, and there are veterinarians who employ it. A recent case report in the Journal of the American Veterinary Medical Association (JAVMA) discusses the lack of evidence supporting the use of bloodroot and illustrates the significant harm these products can do.

Childress, MO. Burgess, RC. Holland, CH. Gelb, HR. Consequences of intratumoral injection of a herbal preparation containing bloodroot (Sanguinaria canadensis) extract in two dogs. Journal of the American Veterinary Medical Association 2011;239(3):374-379.

The report discusses two dogs, belonging to the same owner, who had Neoplasene injected into skin tumors. The first, a 2 year old golden retriever, had a benign tumor about 2cm in diameter. Such masses usually cause no problem for dogs, but if they are disturbing to owners or if they become injured or infected, they can be easily removed surgically, which is curative. Unfortunately, the treating veterinarian elected to inject the mass with Neoplasene. Six days later, the tumor had become bruised and much larger. The veterinarian instructed the client to give an oral homeopathic remedy to reduce the swelling of the tumor (which, given the mountain of evidence that homeopathy is nothing more than water and a bit of placebo effect, cannot reasonably viewed as an acceptable standard of care). After the swelling failed to resolve following drainage and bandaging, the pet was taken to the hospital of the veterinary medical school at Purdue University. By this time the benign 2cm diameter mass had become a 6cm area of severely inflammed and necrotic (dead) tissue.

The dog had surgery to remove the mass and a margin of healthy tissue around it, which involved a very extensive surgical procedure. After many weeks involving several additional surgical procedures and physical therapy to treat the loss of mobility caused by the large wound, the patient eventually made a full recovery.

The second patient discussed in the report, owned by the same client and treated by the same original veterinarian as the first dog, also had bloodroot injected into a benign tumor. A smaller amount of Neoplasene was used, and it appears that some of this leaked out after the injection. As a consequence of this, or perhaps of the variability in unregulated herbal products, the tissue reaction was not as severe as in the first patient. When the mass was surgically removed, an area of inflammation and tissue necrosis was observed near but not in the tumor. Luckily, this dog experienced minimal complications.

Clearly, complications can occur with any medication or treatment that has a measurable physiological effect. Anything that has no possibility of any side effects isn’t doing anything! And it is important to remember that anecdotes cannot be used to prove either the safety or the efficacy of a treatment. Anecdotes of benefit provide only enough evidence to justify more rigorous, systematic testing, not proof that a therapy works. In the majority of cases, such anecdotes turn out not to be accurate when more objective testing is done. Cases in which harm may have resulted from a treatment also cannot prove the treatment is unsafe. They do, however, provide reason to be cautious, and they raise the level of supportive evidence of benefit that should be expected prior to employing the treatment. Medicine is always about balancing the urgency of intervening in a patient’s condition with the available information about the risks and benefits of the intervention.

In the case of bloodroot, there is limited preclinical evidence to suggest it might be a useful treatment. It does kill cancer cells, but so does bleach, which is obviously not a good candidate for use as a medicine. The evidence that bloodroot kills cancer cells and spares healthy tissues is weak and contradicted by numerous cases of obvious tissue damage following application of the chemical. And there simply are no clinical studies to indicate a benefit in actual patients, much less a benefit greater than the potential risks. So we are left with anecdotes about bloodroot curing patients, which are of limited value as such anecdotes are often wrong for many reasons, and anecdotes of patients suffering severe, sometimes disfiguring or disabling injury after using it. Severe injury may not always happen, but it is an extreme risk to take when there is no real reason to expect the treatment has any benefit. Both of these patients would have been effectively cured, with much less suffering, injury, and expense for the owner, if they had been treated with conventional surgery rather than bloodroot.

Given the current state of the evidence, it is irresponsible of veterinarians to use bloodroot products on their patients. And in my opinion it is absolutely unethical for companies and individuals to profit from marketing these remedies without investing the resources in proper clinical studies to prove that they can be used safely and that they actually benefit patients. As I have discussed many times, herbal remedies are likely the most promising area of alternative medicine in which we will hopefully find effective medicines. But until they have been rigorously tested, and until they are regulated as stringently as pharmaceuticals, they are a dangerous gamble with our pets’ health and cannot reasonably be viewed as an alternative to established conventional treatments. Just as the pharmaceutical industry must be carefully watched to constrain the bad behavior that the profit motive can generate, so the herbal medicine industry cannot be trusted to provide trustworthy information and safe and effective remedies without much more oversight that it currently receives.

 

 

 

Posted in Herbs and Supplements | 92 Comments

Holistic Anesthesia for Dogs and Cats

Posted on July 20, 2011 by skeptvet

In a bit of advertising on his blog, a prominent alternative veterinary medicine advocate recently discussed the case of a 15 year old dog that reportedly had heart disease and dental disease and had come to see this doctor because the client’s regular veterinarian felt the risk of anesthesia for dentistry outweighed the benefits in this patient. Few details are provided, but our hero claims to have determined that the heart condition did not require medication and could be managed with “natural therapies” (which likely means there was a heart murmur but no true heart disease, since there are no “natural” substitutes for real medication when there is real heart disease). The author then claims that he was able to successfully treat the dental disease with “holistic anesthesia,” which left the patient “acting like a puppy again.”

I am certainly a proponent of proper dental care, and I applaud the author for taking the position of mainstream veterinary medicine that proper dental care requires general anesthesia in our pets. This is a more controversial idea in alternative medicine circles than in the profession as a whole. And I certainly oppose the inappropriate use of potent heart medications, which sounds like it may have occurred in this case.  However, the core message of this article seems to be that conventional doctors are inappropriately frightened by anesthesia in older pets and that such anesthesia can be done more safely if it is “holistic.” Having never heard the term “holistic anesthesia” before, I was curious what it might mean and whether there is any evidence that it is safer than conventional anesthetic practices.

As I have already discussed previously, “holistic” is one of those vacuous marketing terms that means whatever the speaker wants it to mean or nothing at all, like “natural” or “integrative.” I suspected the phrase “holistic anesthesia” simply meant ordinary anesthesia with some herbs, homeopathy, acupuncture, or other unproven or bogus methods added on and then falsely promoted as somehow safer than conventional anesthetic practices. And, that is pretty much what I found, though I was surprised that it is also sometimes used to refer to practices indistinguishable from conventional anesthetic methods.

The author of the heartwarming story about the old poodle advertises his “holistic” approach to anesthesia this way on his web site:

No More Anesthetic Worries
Surgery can be scary, and we know that you may be a bit nervous about anesthesia. That’s why your pet will receive a comprehensive physical examination prior to every surgery. Blood and urine tests will also be done when needed to minimize the risk associated with anesthesia. And to keep your pet’s chances of anesthetic complications to a minimum, we only use isoflurane gas. It’s a bit more expensive, but it’s the safest anesthetic available.

Your pet is also monitored by a veterinary assistant and 3 monitoring machines which monitors: respiratory rate, heart rate, pulse oximetry and body temperature.

No surgery is routine at [We Make Stuff Up] Animal Hospital. You want the best for your pet, and so do we! And for those owners who are a bit nervous about anesthesia, or who wish to minimize anesthetic complications in their pets, we offer holistic anesthesia to allow for a safer procedure and quicker recovery time.

Wow! What a radical departure from conventional anesthetic practices! Who would have thought of doing a physical examination or laboratory tests before anesthesia, using the cutting edge isoflurane gas anesthetic, monitoring the patient under anesthesia, or treating each patient as a unique individual? Oh, wait…How about EVERYBODY!!! Ok, maybe not everybody, since there are undoubtedly some incompetent veterinarians in practice. But these practices are standard in conventional veterinary medicine and have been since I went to vet school over a decade ago. To advertise them as if they were somehow superior, “holistic” practices is deceitful rubbish, purely marketing driven. Is this really all there is to “holistic anesthesia?” Well, there might be a bit more to it.

The rich mine of nonsense that is the American Holistic Veterinary Medical Association (AHVMA) web site provides two articles from the AHVMA “journal” that go into a bit more detail.

Winter, W. Holistic anesthesia and surgery Part 1. Journal of the American Holistic Veterinary Medical Association 1999;18(2):33-36.

Winter, W. Holistic anesthesia and surgery Part 2. Journal of the American Holistic Veterinary Medical Association 1999;18(3):19-23.

The tone of these articles is unremittingly arrogant, self-aggrandizing, and hostile to conventional veterinary medicine, and the information provided is entirely opinion, with no effort to support any assertions with scientific evidence. For example:

When you need it, surgery is good. It is one of the two only good things going for allopaths. When used properly, modern equipment, drugs, and techniques are approaching the sacred, magical healing we see in Shamanism.

We holistic types get to use surgery too, but there are things we have to take into consideration if we want to claim it as a holistic modality (God, I love using the word “modality”). Sometimes it really is a pain to have a conscience. It is that weight we feel once we are “enlightened.”

Now, the article is twelve years old and written by a now-retired 1975 veterinary school graduate. So one can reasonably argue that it is not representative of what contemporary AHVMA members and other self-proclaimed “holistic” practitioners believe. However, it is the only published discussion of “holistic anesthesia” in the veterinary field, and it shares with the blog article mentioned above both the underlying tone and the absence of any reference to objective scientific evidence. Without some clearer definition of what is meant by “holistic anesthesia,” and without a specific repudiation on the part of the AHVMA and individual members, one might reasonably assume that the principles articulated here are still accepted by proponents of this purported special anesthetic approach.

The first claim Dr. Winter makes about “holistic” surgery and anesthesia is that many of the procedures conventional veterinarians perform are, or should be, unnecessary once the conditions that necessitate them are prevented or successfully treated with alternative methods. Prevention is certainly preferable to treatment of almost any disease, and contrary to the mythology and advertising of alternative medicine, this is an accepted principle in all veterinary medicine. Similarly, he goes on to claim that it is “holistic” to do the safest, least invasive procedure that will yield the desired outcome and that the cost of the procedure and overall condition of the patient should be considered. This is about as radical and unconventional line of thought as the advertising cited above, which is to say it is banal and universally accepted.

Dr. Winter then describes his preoperative routine. Interestingly, he specifically recommends avoiding alternative therapies before anesthetics, though not for the reason you might expect:

Rescue Remedy can be used preop but should be used sparingly as it may interfere with anesthesia. The same is definitely true of using Arnica pre-op. I never give it immediately before surgery. Since anesthetics are “toxic,” many of the good herbs, homeopathics, and flower essences are contraindicated. More anesthetic will be required and the animal will wake up too soon. Use these fine medicines later, after surgery.

Ah, so the “good” natural remedies interfere with the “toxic” anesthetics, so a holistic anesthetic approach should begin with only the same poisons conventional veterinarians employ for anesthesia. Hmm…

He then goes on with some more radical and counterculture notions such as reading the patient’s record and studying the specific procedure before performing it, referring cases beyond one’s expertise to specialists, trying to avoid interrupting surgical procedures, and so on. All revelations to most veterinary surgeons, no doubt. However, Dr. Winter does introduce a few concepts I will admit to not having been taught in vet school:

Surgeries also should be done in the morning to catch the best biorhythms… The holistic surgeon is always aware of moods, the overall feeling of the day, and whether it is a “good surgery day” or a “bad surgery day.” If the feeling of the staff, room or schedule feels off, it is much better to take a break, regroup, and reconsider the pace. In the worst case scenario, stop for the day and reschedule.

Good and true holistic clients will totally understand and even be grateful. I have also learned to read the body language and the words of each client as they bring in their animal for surgery. If you perceive any negativity, especially hostility or an ominous premonition, sit right down with them and talk about alternatives. Don’t cut on an animal if the owner is against you; it is very powerful and should be honored.

I have learned to benefit from cleansing the surgical rooms psychically and spiritually using smudges, candles, herbs, and other processes.

I will admit, it hasn’t occurred to me to cancel surgery if the staff or owner happen to be in a bad mood or to cleanse the surgical room psychically with incense to improve the safety of anesthetic and surgical procedures. Something to think about.

The bulk of the discussion of anesthesia per se emphasizes the use of injectable anesthetics and avoiding gas anesthetics, which he describes as “part of an expensive racket.” He also emphasizes speed above all other considerations in reducing surgical and anesthetic risks. These are opinions, mostly without scientific justification, that say more about the era in which the author was trained than about anything uniquely “holistic,” and I suspect they are not widely held by contemporary alternative practitioners. The same is likely true for the outdated sterile technique advice, the belief that pain should be largely left untreated because it forces the patient to “rest” and thus aids healing, and much of the other “Common Man technology” and techniques Dr. Winter recommends. However, what is common to these articles and the writing of younger advocates of “holistic” medicine is the blithe reliance on individual opinion and experience as a justification for pronouncements about what is or is not safe and effective care, the lack of interest in scientific evidence, and the continual derogation of conventional veterinary medicine.

Of course, in order to make so-called “holistic anesthesia” detectably different from conventional anesthesia, it is necessary to add a variety of unproven therapies to the usual treatment, and Dr. Winter certainly does this. Needless to say, he provides no evidence whatsoever to justify these practices:

I augment the natural raw diet, which we have discussed in other articles or which can be found in Dr. Pitcairn’s book, with extra chopped greens every day and bits of raw liver, 1-5 raw eggs (with shell)/ week helps too. For minerals I use Vitamineral Mix (see Pitcairn) varying from 1/2 teaspoon to several tablespoons daily and especially sea kelp, 1/8-1/2 teaspoon daily. I add Vitamin C, 1000mg/day for a cat and up to three times that amount for a large dog, and Vitamin E, 400 iu/week for a cat amd up to 400 iu/day for a large dog. My personal favorite herb for bone healing is Comfrey and I usually use dried herb added to the food. Herb books list many other bone setting herbs that will work as well. Continue all supplements for several months after healing. This diet and supplement regimen should be used in all trauma cases regardless of type of fixation. I also add specific homeopathics, flower essences, sometimes acupuncture, and sometimes magnets, depending upon the case…

Herbal medicine is at its zenith when it comes to wound dressing. Who has not applied Aloe Vera to a wound? It is satisfying, it soothes, the client loves it (usually), and it works. I have a veterinary book, out of print now, by Richard Holliday, DVM, which shows hundreds of pictures of wounds allowed to heal open, naturally with some debridement and with Aloe Vera. I have used the book and its pictures many times to convince an owner that natural healing will really work.

After all, who needs clinical research when you have pictures to prove something works?

Finally, Dr. Winter provides some marvelous examples of cognitive dissonance and the misunderstood, even persecuted attitude that often characterizes the writing of those promoting approaches widely believed to be nonsense. Like so much else in these articles, of course, this is not uniquely “holistic,” but it does reveal the nature of a perspective completely immune to evidence or any possibility that the author might be mistaken.

In closing, there is a problem with all that I have just said, and it applies equally to all holistic services. That is when things do not work out in a rapid, linear, positive manner with full healing. It will not take long for some owners (or did they all come to me and me alone?) to go to another non-holistic vet who will assure them that had they chosen any other option than the one you did, the animal would have healed perfectly! I call this Double Jeopardy, because you can be a loser either way. If you are afraid to try natural healing, you lose because you can never be brave enough to be holistic, but if you try it, and for whatever reason (almost always due to bad owner post-op care, not you) there is a problem, you will be the scum of the universe. You have to follow your heart here. Holistic medicine is not for the cowardly and the weak…

Other vets are very threatened by this simple healing style, primarily because they have never tried it and they may truly think you are crazy. I know from firsthand experience that they will often report you to State Boards for being incompetent if they get involved with a case you are healing this way, so be careful. Stitching or bandaging some wounds strictly for legal reasons could be considered holistic too. We live in a crazy world.

So if it doesn’t get better, it’s not your fault it’s probably the owner’s. But other veterinarians are likely to blame the bad outcome on your idiosyncratic and unconventional techniques (while, of course, holistic veterinarians would never claim that bad outcomes are the result of conventional medical practices and that they could have been avoided if the owner had followed a superior holistic technique). Other vets only object, of course, because they don’t understand, they haven’t tried your methods themselves, or they are “threatened.” So you have to follow your heart regardless of the apparent outcome of the evidence, though if legally threatened it can be “holistic” to do something incompatible with what you really believe is the best care.

Bottome Line
“Holistic anesthesia” is a meaningless, “feel-good” marketing term. In many cases, it is simply a rebranding of conventional anesthetic and surgical practices. In others, it is the addition of bogus or unproven alternative therapies to conventional care, with the credit for good results always going to the alternative methods and the blame for bad results always attributed to the conventional drugs or procedures. The use of the term, however, is a warning sign of a philosophical approach fundamentally hostile to science and scientific evidence and willing to alternative approaches by means of denigrating conventional medicine regardless of the lack of evidence to support claims of superior safety and efficacy.

Posted in General, Miscellaneous CAVM | 9 Comments

Placebo Treatment for Asthma: Works for the Mind but not the Lungs

Posted on July 18, 2011 by skeptvet

Note: I originally wrote this for Science-Based Medicine, but Dr. David Gorski has posted a far more detailed review of the study, which I encourage everyone to read, so I am just posting my thoughts on the subject here.

The placebo effect is a controversial, and in my opinion deeply misunderstood, phenomenon. At Science-Based Medicine, there has been plenty of discussion and debate on the subject before, and different authors have slightly different perspectives (for example, Drs. Novella, Gorski,Ramey and pharmacist Scott Gavura). A recent study in the New England Journal of Medicine (NEJM) serves to illustrate nicely my own view of the nature of this phenomenon, so I thought I’d have a go at characterizing it.

The placebo effect is often claimed to be a real improvement in a patient’s disease that is caused by an inert treatment, purportedly through the power of the mind to heal the body when the patient believes they are receiving an effective therapy. This is certainly how alternative medicine advocates characterize it when scientific studies identify their interventions as no more effective than placebos. However, in my opinion this is not an accurate characterization of the placebo effect.

There are many non-specific treatment effects seen in clinical trials, including the placebo, and all create the perception and appearance of improvement in patients given a fake therapy which is actually doing nothing to alter the underlying medical condition causing the patients’ symptoms. Some such effects are artifacts of the research setting, like the Hawthorne Effect. In this phenomenon, people take better care of themselves when they are participating in a research study and being closely monitored, and so they tend to improve regardless of whether the treatment being studies is helping them or not.

Other non-specific treatment effects, like the placebo, are illusions created by the belief and expectations of the patient or investigators. They do not represent an unlocking of deep and powerful forces of mind over body. They simply trick us into feeling or looking better when our condition is really unchanged.  

One can argue, of course, that if a patient perceives inherently subjective symptoms, such as pain or nausea, to be improved, then they must really be improved. There is some truth to this, but the argument can easily lead to exaggerating the benefits of fake treatments which don’t actually affect the patient’s physical health. Homeopathy may make a person experience his or her pain less intensely, but a real medicine will achieve this, usually to a greater extent than a placebo, by actually reducing the pain generated in the body as well as the perception of pain in the mind. Taking advantage of placebo affects that accompany all real medical treatments is fair enough, but substituting alternative therapies that are nothing but placebo for real medicine is not in the best interest of patients.

And this is doubly true for veterinary patients. Lacking beliefs and expectations about their health, my patients cannot experience the placebo effect per se. Some improvement in symptoms may occur as a result of conditioning and the human contact associated with  therapy, but in general animals don’t enjoy the “benefit” of being fooled by their own minds into thinking an inert treatment has made them better. Unfortunately, animal owners and veterinarians are subject to being misled by non-specific treatment effects, and the “placebo-by-proxy” effect is quite potent. It creates an especially dangerous situation in which an animal’s caretakers believe they are helping the patient and the combination of cognitive errors and cognitive dissonance prevents them from appreciating that the animal’s condition is actually not improved.

The new NEJM paper demonstrates both how powerfully our own beliefs and expectations can fool us into feeling better and how careful we must be to distinguish this from actual improvement in our condition. The full article is behind a paywall, but a short summary is available.

Wechsler, ME. Kelley, JM. Ph.D. Boyd, IOE. Dutile,S. Marigowda, G. Kirsch, I. Israel, E. Kaptchuk, TJ. Active albuterol or placebo, sham acupuncture, or no intervention in asthma. N Engl J Med 2011; 365:119-126

Forty-six patients with asthma were randomly assigned to receive no treatment, or to treatment with an inhaled bronchodilator (albuterol, which opens up airways constricted by asthma), a placebo identical to the bronchodilator treatment, and sham acupuncture presented as “real” acupuncture (whatever that is). All patients were rotated through all the treatments and assessed after each, and the patients and investigators were blinded to the treatments insofar as possible. Obviously, patients and researchers could tell the difference between no treatment, an inhaler, and acupuncture. And as is always the case in studies of acupuncture, the acupuncturist undoubtedly knew that they weren’t providing what they would call genuine acupuncture treatment.

The patients were evaluated both in terms of their own perceptions of any improvement in their symptoms as well as an objective measure of their respiratory function. When given no treatment at all, patients reported an improvement in their symptoms of 21%. This likely represents a variety of non-specific treatment effects, such as the natural history of the disease, the aforementioned Hawthorne Effect, and so on. It also illustrates the value of a no-treatment group in clinical trials, when it is ethically possible to have one. This is an element of clinical trial design that sometimes gets inadequate attention in discussions of the pitfalls of medical research, though there is evidence that when such groups are included, the purportedly powerful effects of the placebo phenomenon become less impressive.

There was no difference in the improvement perceived by patients regardless of which of the other treatments they received. Between 45-50% improvement was reported after treatment with the albuterol inhaler, placebo inhaler, and sham acupuncture. So patients experienced nearly twice as much benefit from some treatment as from no treatment, but it made no difference whether the treatment was real or inert. This would seem to suggest that the placebo is a potent therapy and as good as a physiologically active medicine. After all, asthma symptoms are quite recognizable and uncomfortable, so it seems unlikely that such high rates of improvement would be only a function of the patients’ imagination. Perhaps there is something to this mind-body medicine idea, and alternative therapies really can make us better through placebo effects even if they don’t have any other effects?

Well, not so fast. In addition to asking the patients how they felt after each treatment, the investigators also measured their lung function, using an instrument that records, among other data, how much air the patients could force out of their lungs in a given period of time. It turns out that this objective measure showed a 20% improvement with the bronchodilator inhaler, but a significantly lower 7% improvement with the inert therapies or no treatment at all. So while the patients couldn’t tell the difference between real and fake therapies, their lungs certainly could.

This illustrates what I think is the key point to understand about the placebo effect: It can make us feel better without actually affecting our physical health. In any discussion of the placebo effect, we must bear this fact in mind. There is no magical power of mind over body involved. Placebo treatments affect our perceptions of our symptoms, but they do not improve our underlying medical condition.

It is a desirable and appropriate for doctors to make their patients feel better, but it is not enough to do so only in ways that leave the physical health of the patient fundamentally unchanged. We owe it to our patients to apply rigorous scientific methods to investigating our therapies and to developing interventions which actually treat the cause of the symptoms, not just the patients’ perceptions of them.

There is nothing wrong with taking advantage of placebo effects that inevitably accompany therapeutic interactions. But I believe it is unethical to employ therapies which are demonstrated to have only placebo effects, particularly when interventions that actually treat the underlying medical condition are available. And as a veterinarian, I am strongly opposed to using treatments that clearly work in humans only through belief and expectation, since these are very likely to mislead owners into believing the therapy is working without actually benefitting the patient.

This study illustrates both the power of the placebo effect to make us experience marked improvements in seemingly undeniable disease symptoms and also the powerlessness of the placebo effect to improve our physical health. It shows how easy it is for us to be fooled concerning the effectiveness of a medical therapy by our personal experiences as patients and doctors, as well as how easily a clinical study can generate the false impression of a beneficial therapeutic effect if placebo and no-treatment controls and objective outcome measures are not employed. Finally, it provides a point of evidence against the currently popular contention that even though some alternative therapies cannot be shown to have effects greater than placebo, they can be viewed as having real benefits by means of the placebo effect and the power of mind over body. At best, placebo effects can alter our perceptions of our symptoms to reduce our discomfort. But they cannot fundamentally improve our physical health, and there is real danger in believing they can if it leads us to rely on therapies that are only placebos.

Posted in General | 6 Comments

Prolotherapy for Dogs and Cats

Posted on July 14, 2011 by skeptvet

What Is It?
Prolotherapy is a commonly offered alternative treatment for joint, connective tissue, and back pain. The practice consists of injecting substances into painful or dysfunctional joints and connective tissue with the intent of relieving discomfort and restoring function. There is a wide range of substances that are used with a much variation among practitioners of prolotherapy. Examples of these substances include: dextrose or other sugars, Vitamin B12, local anesthetic agents, a wide variety of herbal products, homeopathic remedies, zinc sulfate, the patient’s own blood, and hundreds of others. Often, cocktails of multiple substances are used based on the individual preferences of the practitioner.

The theoretical rationale for the practice is that the substances injected into damaged joints or connective tissue will cause inflammation and chemical or cellular activity that will lead to repair of the affected tissues. (1,2) The logic of this theory is questionable. For one thing, inflammation is a normal physiologic response to tissue injury, and is already present in damaged tissues and joints. However, the evidence is clear that excessive or prolonged inflammation interferes with healing. Arthritis, a disorder prolotherapy is supposed to treat, is by definition chronic inflammation of joints, and this inflammation is known to cause much of the pain and tissue damage associated with arthritis. In general, excessive or chronic inflammation does more harm than good, and many conventional and alternative medical therapies are intended to reduce the deleterious effects of inflammation, so deliberately causing it to induce healing seems a dubious approach.

There are theoretical arguments involving the stimulation of cells involved in healing, such as fibroblasts, or the release of growth factors and other substances that are associated with tissue repair, which might plausibly explain how prolotherapy could be beneficial. However, the in vitro research to date suggests the effects of prolotherapy agents on tissues are broad and non-specific, and such effects are as likely to be harmful as beneficial. The underlying theory is questionable but not impossible. However, without a clearly demonstrated physiological mechanism and consistent animal model and clinical research evidence, it is not enough to justify the use of this therapy or the claims often made for it.

Does It Work?
There have been a number of studies and reviews investigating the use of prolotherapy in humans, and more are ongoing. Overall, the evidence has been mixed and of generally low quality. A Cochrane Review of prolotherapy for lower back pain examined five studies involving 366 people.(3) The review concluded,

There is conflicting evidence regarding the efficacy of prolotherapy injections for patients with chronic low-back pain. When used alone, prolotherapy is not an effective treatment for chronic low-back pain. When combined with spinal manipulation, exercise, and other co-interventions, prolotherapy may improve chronic low-back pain and disability. Conclusions are confounded by clinical heterogeneity amongst studies and by the presence of co-interventions.

The insurance companies Aetna and Cigna and the Veterans Administration have published extensive reviews of the scientific literature on prolotherapy.(4,5,6) The reviews conclude:

Aetna:

Aetna considers prolotherapy (also known as proliferant therapy or proliferation therapy) experimental and investigational for any indications because there is inadequate evidence of its effectiveness.


Cigna:

Medical studies in the literature evaluating this technology present few randomized, double-blind clinical trials that had adequate sample size and controls and that used objective outcome measures. Additionally, studies have not successfully supported the use of prolotherapy as an effective treatment for joint or ligament instability. Furthermore, several systematic reviews, a Cochrane review, and technology assessments have reported prolotherapy injections have not been proven to be as effective as or more effective than placebo injections. Additional randomized studies are needed to evaluate the efficacy of prolotherapy for joint or ligament instability. The evidence in the peer-reviewed, published scientific literature is insufficient to support the use of prolotherapy for any therapeutic indication.

 

Veterans Administration

Although proponents have advocated the use of prolotherapy for a range of indications, relatively few clinical uses have been studied systematically or published in the peer-reviewed literature. Results of the most recent systematic reviews are inconclusive for demonstrating the effectiveness of prolotherapy for treatment of musculoskeletal pain, and new evidence from case series would not alter these conclusions. The majority of published experimental studies have included conservative therapy with prolotherapy for relief of chronic low back pain, and to a lesser extent, osteoarthritis of the knee with varying results. Sample sizes have been insufficient on which to base national policy decisions.

These reviews are particularly useful as sources of references to studies examining prolotherapy. Reviewing the studies cited in these summaries, it is clear that the majority of positive results stem from trials without proper controls: randomization of subjects, placebo or no treatment control groups, proper blinding, etc. And because the agents used and other aspects of the treatments are inconsistent between studies, it is difficult to compare studies or to generalize from one study to a different prolotherapy treatment approach, and it is impossible to combine small studies in meta-analyses that might have greater power to determine if the treatment is truly effective.

It  is often the case that smaller and less rigorously designed studies tend to have positive conclusions. As the quality and quantity of research improves, many of these results turn out not to be trustworthy. Prolotherapy in humans is currently supported by a limited quantity of low-quality research. Until stronger evidence accumulates, if it does, the practice should be viewed as an experimental therapy of unknown benefits and reserved for circumstances in which conservative management and established conventional therapies are unsuccessful.

As is also often the case, there are absolutely no rigorous, controlled clinical studies of prolotherapy in dogs and cats. The use of this approach in pets is based entirely on anecdotal evidence, which is highly unreliable, and on extrapolation from human medicine, in which the practice has little supportive evidence and is not widely accepted as a legitimate therapy. Prolotherapy might be justifiable as an experimental intervention in cases in which better studied therapies with more established physiological rationales have failed or cannot be used, but it should not be marketed with strong claims of “proven” benefits, and it should not be used in lieu of conventional treatment.

 Is it Safe?
Any injection into a joint must be done with careful attention to technique to avoid introducing infection or damaging tissues, and sedation may be necessary for such treatments, so these are risks associated with but not unique to prolotherapy treatment of joints. In humans, there have been limited efforts to assess the risks of prolotherapy. One survey of practitioners of this treatment has been reported.(7)

Dagenias et al. (2006) studied the effects and adverse events related to prolotherapy for back and neck pain. The authors conducted a practitioner postal survey evaluating prolotherapy for back and neck pain in the United States and Canada. Surveys were mailed to members of the American Academy of Orthopaedic Medicine (AAOM) and the American College of Osteopathic Pain Management and Sclerotherapy (ACOPMS), both closely affiliated with prolotherapy conference, in addition to nonmembers attending the 2004 AAOM annual conference. A 50% response rate was obtained. The authors published that the side effect with the highest estimated median prevalence was temporary post-injection pain (70%), stiffness (25%), bruising (5%), and temporary numbness (1%). The most commonly reported adverse events (total of 472) were spinal headache (n=164), pneumothorax (n=123), temporary systemic reactions (n=73) and nerve damage (n=54). A total of 69 adverse events required hospitalization, and five resulted in permanent injury, secondary to nerve damage. Almost 98% of the respondents held MD or DO degrees, and 83% were board certified in related disciplines. The authors concluded that to better assess the true risk of adverse events related to prolotherapy, further well-designed clinical trials that are designed to over-come bias inherent to practitioner surveys are needed.

Overall, prolotherapy likely presents a low to moderate risk depending on the agents used and the skill and experience of the practitioner.

Bottom Line
Prolotherapy is a purported treatment for connective tissue and joint pain and disability. It involves injecting substances which induce inflammation and other chemical and cellular reactions into affected tissues. These reactions are theorized to relieve pain and improve function. The logic of this theory is questionable, and no clear mechanism for beneficial effects from prolotherapy has been described, but it is possible that the theory could be valid.

The clinical research on prolotherapy in humans is generally of low quality and results have been mixed. There is great variation in the techniques used by different investigators, so it is difficult to compare or generalize between studies.

There is virtually no controlled research investigating prolotherapy in companion animals, and all claims made for safety and efficacy in these species are based solely on anecdotal evidence.

The use of proltherapy in pets should be viewed as experimental with unknown risks and benefits. Such treatments should be reserved for patients that have significant symptoms that have failed to respond or cannot be treated by conventional means.

References
1. Banks, A.R. A rationale for prolotherapy. Journal of Orthopaedic Medicine. 1991;13(3). Accessed at http://www.prolotherapy.com/articles/banks.htm July 13, 2011.

2. Robinson, NG. Prolotherapy for pain. 2007. Accessed    at http://csuvets.colostate.edu/pain/Articlespdf/Prolotherapy%20for%20Pain.pdf July 13, 2011.

3. Dagenais S, Yelland MJ, Del Mar C, Schoene ML. Prolotherapy injections for chronic low-back pain. Cochrane Database of Systematic Reviews 2007, Issue 2.

4. Aetna. Clinical Policy Bulletin: Prolotherapy. Last revised May 24, 2011. Accessed at http://www.aetna.com/cpb/medical/data/200_299/0207.html July 13, 2011.

5. Cigna HealthCare Coverage Position: Prolotherapy. Last revised December 15, 2006. Accessed at http://stage.cigna.com/health/provider/medical/procedural/coverage_positions/medical/mm_0006_coveragepositioncriteria_prolotherapy.pdf July 13, 2011.

6. Adams E. Bibliography: Prolotherapy for musculoskeletal pain. Boston, MA: Veterans Administration Technology Assessment Program (VATAP); April 2008.

7. Dagenais S, Ogunseitan O, Haldeman S, Wooley JR, Newcomb RL. Side effects and adverse events related to intraligamentous injection of sclerosing solutions (prolotherapy) for back and neck pain: A survey of practitioners. Arch Phys Med Rehabil. 2006 Jul;87(7):909-13.

Posted in General | 13 Comments

Pressure Wraps for Anxiety in Dogs

Posted on July 10, 2011 by skeptvet

Here is another excellent, informative post from contributing author and dog trainer Kyzyl.

Pressure Wraps for Anxiety and Fearful Behavior

Fear is a set of evolutionarily important behaviors for animals.  Fear often keeps animals alive in a dangerous world by teaching them to avoid things that could bring about their untimely end.  However, when fearfulness runs out of control or is coupled with common, innocuous events, it can become a serious behavior problem for pets and their owners.  Whether it is associated with specific triggers, such as car rides, thunderstorms, and veterinary visits, or generalized, excessive anxiety and fearfulness can intensify to the point where normal functioning becomes impossible, and pets can act out in extreme ways including aggressively, urinating and defecating on themselves, or shutting down completely when forced into situations that trigger fear. 

If your dog has moderate or severe problems with fear, there are a limited number of treatments to help alleviate anxiety including behavior modification and drug therapy. Behavior modification, when done effectively, is very successful at alleviating considerable amounts of stress due to specific stimuli.  Behavior modification plans for fearful dogs often consist of two techniques: counter conditioning and systematic desensitization. These techniques change behavior by changing the underlying emotional state of the dog, therefore relieving the stress and anxiety of the fear-based behavior (8). In severe cases, vets might also prescribe a sedative to help with specific situations like grooming or veterinary visits or general anxiety or an anti-anxiety medication to reduce fear enough to improve the patient’s quality of life and allow behavior modification a chance to work.

However, behavior modification techniques are often very difficult for owners to execute correctly.  Behavior modification tools require training skill and time, neither or which average owners can often provide.  And many owners are also very reluctant to medicate their pets for behavior problems. 

As a result, many owners and trainers have turned to alternative therapies that promise great results for treating phobic behavior, one of which is pressure wraps.  Commercial pressure wraps (the Anxiety Wrap® and the ThundershirtTM) use elastic fabric and velcro to create a tight-fitting garment that is worn during anxiety-causing events.  When fitted properly, the garment creates distributed pressure over the chest, sides, and back that supposedly has a calming effect.

How do they work?  According to the ThundershirtTM website, several reasons were listed as evidence for why the product’s gentle pressure worked to calm anxious behavior (10).  These include a reference to people with autism using pressure to relieve anxiety, swaddling as a method of calming upset babies, acupressure, and TTouch practitioners using pressure to address anxiety. These are not high-quality sources of evidence, but interesting ideas to consider none the less. 

While there is little research on touch and pressure therapies in dogs, the effects of these therapies have been studied in humans and other mammals.  Touch is critical for normal development of infant rats and humans and profoundly affects our social interactions (1,2,9).   We know that touch, especially deep touch such as a hug, releases endorphins that promote relief from pain and a sense of well-being and self-reported improvement of symptoms of compulsive disorders and depression in humans(1,2).  

Massage has long been used to successfully address issues with musculoskeletal pain,   but when used to treat anxiety in people results have been both positive and negative leading to an inconclusive answer on whether or not it is useful treatment for anxiety (1,3,4,5). 

Knowing that generally pressure and touch have effects on people, and by extension pets, makes evaluating claims of specific systems that employ it very difficult.  Firstly, since general touching provides many of the benefits claimed through the system, it may be that the specific motions, actions, or places suggested by different systems of touching are not as important as the act of touching itself.  Without controlling for these general effects, one can never be sure if positive results are due to the general effects or more specific effects of the system’s protocol. 

Other modalities supporting pressure for anxiety relief, such as acupressure and Tellington TTouch®, have very little supporting evidence.  Acupressure, a variation on acupuncture where acu-points are pressed to influence the flow of qi, has been addressed several times on this blog (12).  In the great majority of cases, it has no specific effect beyond placebo or sham treatments.  Tellington TTouch® combines specific touches with exercises in order to, as its website claims, “activate the function of cells and awaken cellular intelligence” (16).  (Though anxiety and fear may be a big problem for a dog, I doubt it has much to do with how ‘intelligent’ its cells are.)  Despite the complicated protocols and mystical thinking called for by both, no evidence these modalities work beyond the general effects of touching.

The effects of touch seem to be best studied in systems with human contact, touch by a human, and there is no reason to think that touching by inanimate objects would have the same effects.  A supporting example referenced on the ThundershirtTM website illustrates this: swaddling babies.  Is it the tight wrapping that calms the child, or the warm touch of its mother?  These claims should be evaluated separately to determine the effectiveness of a pressure wrap.

What is the specific evidence for pressure wraps?  People with autism report anecdotally feeling at ease when experiencing pressure from inanimate objects. Dr. Temple Grandin, who is referenced on the ThundershirtTM website (10), developed a hugging machine to help her through anxiety related to autism..  This machine allowed the user to control the duration and intensity of pressure applied to his or her body.  In preliminary, uncontrolled trials, both autistic and neurotypical people suffering from anxiety self-reported improvement (6).  Despite initial research being promising, this hypothesis has garnered little support in the scientific literature over the past decade.

However, there are major differences between the hug machine and pressure wraps which are meant to reproduce its calming effects. Pressure wraps apply a constant pressure not under user control.  Also, pressure wraps likely do not produce the same type of deep pressure as the machine.  A pressure wrap, similar to those for dogs, was developed for autistic children seeking to replicate the effects of the machine have not had success in relieving anxiety in stressful situations (ref). 

Several professionals report success in the ‘testimonial’ section of the products’ websites (10), reporting dramatic and immediate improvement of anxious and fearful behavior in dogs wearing these wraps.  They both make fantastic claims that their wraps can correct problems ranging from behaviors associated with phobias to pulling on leash during walks, with very little cited research or concrete numbers to back up these claims.

While these anecdotal reports from professionals certainly justify interest in conducting trials, they do not necessarily support the confident claims made on the product websites.  The problem with anecdotes is that they often only tell the story we want to hear, they don’t describe the truth of a situation.  Humans have very selective memories, often remembering only the details that support a line of thought (conformation bias: 14,15), so that details or cases that don’t support the thought are forgotten or neglected.  Furthermore, companies have great financial motivation to only share extremely successful cases and ignore all the wraps they sold that didn’t work as advertised.  Customers reports in which the wraps didn’t work don’t often make it to the ‘testimonial‘ page, but plenty have shown up in product review pages for third party sites such as Amazon.com, in which 30-40% of reviewers said that the Thundershirt had little or no effect on their dog’s anxiety(11).

Strong evidence for the effectiveness of pressure wraps would come from trials looking at the effect of pressure wraps compared to controls for each of the behavior problems listed. I was unable to find any controlled trials that test for efficacy of pressure wraps for any dog behavior problems, much less the long list of problems each product’s website claimed to solve.  (If you should know of any trials, please let me know.)  Other than one clinical trial still enrolling at Tufts University’s Veterinary School (13), I have found no evidence that either company has attempted to at all test the claims they make for their pressure wraps for dog behavior problems.

So maybe pressure wraps work, and maybe they don’t. If they don’t hurt, why not try them out? The biggest concerning of using a pressure wrap is one of the more dangerous aspects of using alternative therapies: giving up on conventional treatments that do work.  On its website, the ThundershirtTM insists that no training is needed for these wraps to work, simply strap it on and all the behavior problems lessen or go away.  By not engaging in behavior modification, particularly systematic desensitization, the emotional state causing fearful or anxious behavior will never be addressed.  And for this training to work, often times medication must be used to lessen anxiety to a manageable level.  Much like putting a bandaid on an infected sore, simply using the pressure wrap may only serve to mask visible symptoms without curing the underlying infection.  With no real treatment, a pet could continue to quietly suffer from fear or anxiety.

In conclusion, I find no high-quality evidence that pressure wraps, such as the Anxiety Wrap® or ThundershirtTM, help or correct behavior problems including those associated with anxiety or fearfulness.  Their principle idea, that distributed pressure calms the nervous system and relieves behavior problems in dogs, remains an intriguing, yet unsupported, hypothesis.  While pressure wraps are most likely safe to use, they should not be considered a replacement for more conventional treatments such as behavior modification and drug therapy.

 

1.  Fields, T.M. 1998.  Touch Therapy Effects on Development.  International Journal of Behavioral Development 1998 22: 779-797.

2.  Haans, A. and IJsselsteijn, W. 2006. Mediated social touch: a review of current research and future directions. Virtual Reality 9(2-3): 149–159.

3.  Heidt, P. 1981. Effect of therapeutic touch on anxiet level of hospitalized patients. Nusing Research 30(1): 32-37.

4.  Ferrell-Torry, A.T. and Glick, O. J. 1993. The use of therapeutic massage as a nursing intervention to modify anxiety and the perception of cancer pain. Cancer Nursing 16(2): 93-101.

5.  Randolph, G.L. 1984. Therapeutic and physical touch: physiological response to stressful stimuli. Nursing Research 33(1): 33-37.

6.  Grandin, T. 1992. Calming effects of deep touch pressure in patients with autistic disorder, college students, and animals. Journal of Child and Adolescent Psychopharmacology 2(1): 63-72.

7.  LaChappelle, R. 2009. Use of a Pressure Vest to Reduce the Physiological Arousal of People with Profound Intellectual and Physical Disabilities During Routine Nail Care. Thesis. Dept of Occupational Therapy, East Carolina Univ.

8.  Butler, R., Sargisson, R.J., Elliffe, D. 2011. The efficacy of systematic desensitization for treating the separation-related problem behaviour of domestic dogs. Applied Animal Behaviour Science 129: 136–145.

9.  Field, T. 2010. Touch for socioemotional and physical well-being: A review. Developmental Review 30: 367–383.

10.              Thundershirt website: http://www.thundershirt.com/

11.              Amazon product page for Thundershirt by Ovris: http://www.amazon.com/Thundershirt-Dog-Anxiety-Treatment-Large/dp/B0028QK6EY

12.              Acupuncture category on Skeptvet Blog: http://skeptvet.com/Blog/category/acupuncture/

13. Clinical Trials: The use of the Thundershirt to alleviate anxiety in hospitalized canine patients. Cummings School of Veterinary Medicine, Tufts Univ. http://cgi.vet.tufts.edu/clinical_trials/projects/the_use_of_the_thundershirt_to_alleviate_anxiety_in_hospitalized_canine_patients Accessed: 8 July 2011.

14. Conformation Bias, Wikipedia: http://en.wikipedia.org/wiki/Confirmation_bias Accessed: 8 July 2011.

15. SkeptVet. Why We’re Often Wrong. http://www.skeptvet.com/index.php?p=1_13_Why-We-re-Often-Wrong Accessed: 8 July 2011.

16. Tellington TTouch®: What is TTouch®?http://www.ttouch.com/whyTTouch.shtml Accessed: 8 July 2011.

 

 

 

 

 

 

Posted in Guest Posts | 34 Comments

Vitamin K3 (menadione) in Pet Food: Is It Safe?

Posted on July 8, 2011 by skeptvet

One of the most popular fallacies that arises in discussions of pet health is the appeal to nature or naturalistic fallacy. Simply put, this is the notion that what is labeled “natural” is inherently safe, beneficial, or otherwise good, and what is labeled “artificial” is inherently unsafe, harmful, or bad. This argument fails on many levels. For one thing, the distinction between natural and artificial is often quite arbitrary and based on ideology rather than any rational criteria. How could any food crop, which consists of huge, bizarrely
mutated plants that could never survive without cultivation, be natural? For
that matter, how could most breeds of dog be considered natural when they have
been so dramatically altered in form and function by thousands of years of controlled breeding? Is wearing clothes, washing our hands with soap, cooking our food, or really any of the basic health and safety practices we follow routinely natural if we are the only species who employs them?

The appeal to nature fallacy also fails on the simple basis of being demonstrably untrue. Arguably natural things like Salmonella, hookworm, bubonic plague, and uranium are clearly dangerous. And clearly artificial things like vaccines, antibiotics, and modern sewage and water treatment systems are the only reason the majority of human beings gets to live past childhood these days. So whenever the only basis for declaring something
good or bad for your pets appears to be the idea that it is natural or artificial, it is wise to be very skeptical of such claims and look for more reliable evidence.

A perennial example easily found on the Internet is Vitamin K3 (menadione) in pet foods. Vitamin K is an essential nutrient needed in very low levels by dogs and cats. It is required for producing the substances that allow blood to clot and prevent us from bleeding to death from every little scratch. Most rat poisons consist of chemicals that interfere with Vitamin K, and these common and very dangerous poisons frequently lead to dogs coming into the veterinarian’s office with severe, uncontrollable bleeding. Fortunately, in
most cases these patients can be saved, and the cornerstone of their treatment
is Vitamin K replacement.

Most of the Vitamin K dogs and cats need is manufactured by bacteria in the gastrointestinal system and absorbed from there, so dietary requirements are miniscule. The one known exception is that cats fed diets with a high proportion of fish oil in them have developed Vitamin K deficiency and bleeding problems. Since fish as a protein source and fish oil as a supplement are becoming more widespread, it is possible that this problem could be seen more frequently. In general, however, the amount of dietary Vitamin K required by dogs and cats is still very, very small.

Plant and animal sources of Vitamin K include two types, Vitamin K1 and Vitamin K2. Vitamin K3, or menadione, is a synthetic form of Vitamin K. By itself, it has little biological activity, but it can be converted to a more active form by bacteria in the gut and other pathways. It is useful as a Vitamin K supplement in pet foods because it is more stable and tolerates heating better than the other forms of Vitamin K. Advocates of
“natural” medicine and nutrition often claim, however, that unlike these other forms, Vitamin K3 is toxic to dogs and cats. So what is the basis for this?

Of course, the first foundation “natural” medicine advocates use for claiming menadione is harmful and should be replaced with Vitamins K1 or K2 is the appeal to nature fallacy. As I’ve already pointed out, this is a meaningless claim which tells us nothing about the safety of any food or supplement. So what about other, more meaningful forms of evidence?

Well, to begin with, no case of toxic effects from menadione in commercial dog or cat food has ever been substantiated. Millions of pets have been consuming this vitamin for
decades, so if the supplement were to have any significant potential risk, one
would expect many documented cases of harm. This is, at least, the basis
“natural” medicine advocates use to claim that the herbal products and dietary supplements they recommend are safe. Unfortunately, without any systematic effort to monitor for such events the best we can say is that there does not appear to be a large or common risk, though we cannot rule out the possibility of some negative effects in some individuals solely on the basis that such cases have not been reported.

There is some laboratory research and pre-clinical animal studies that look at the safety of menadione. These have found that toxic effects can be seen on isolated cells, rats, and other animal models in the laboratory, but at levels tremendously higher than could ever be achieved by eating foods supplemented with Vitamin K3. This points out another common fallacy employed by so-called “holistic” medicine practitioners, the
notion that chemical compounds are inherently either toxic or safe. The reality
is that toxic effects are a function of the dose or amount of a substance one
is exposed to, the route of exposure, the individual’s susceptibility, and many other factors. Water and oxygen are toxic at high enough doses and under the right circumstances. And deadly natural poisons such as curare and other animal toxins can have beneficial medical uses if handled and dosed appropriately. So it is meaningless to simply label something as
“toxic” and ignore the devil in the details.

It turns out that doses of menadione needed to cause health problems are more than 1000 times greater than could be gotten through food supplementation, and the studies showing toxic effects usually involve injecting the vitamin into animals at high doses, not providing it in food in miniscule amounts. It is true that Vitamin K3 supplements for human use have been banned by the Food and Drug Administration (FDA), however this is because
of the potential for very large exposures when humans irrationally choose to take extreme quantities of dietary supplements. The FDA does permit the use of menadione in animal feeds because the consumers, our pets, are unlikely to make similar mistakes. When the toxic dose is more than can be found in an entire bag of food, the risk of accidental exposure to harmful levels is negligible.

Bottom Line
Under normal circumstances, dogs and cats need extremely small amounts of dietary Vitamin K. At the low levels of supplementation in commercial foods, menadione is a safe source of this Vitamin K. Toxic effects can be seen when enormous quantities are given to an animal or when menadione is used injectably, but there are no documented cases of any harmful effects from dietary supplementation of menadione in commercial pet foods. The three veterinary nutritionists and one veterinary toxicologist I consulted on this
issue all agreed that there is no evidence of any significant risk from menadione in commercial pet foods. The concerns about this supplement seem to stem almost entirely from the appeal to nature fallacy and from the mistaken belief that substances are inherently either safe or toxic regardless of dose or route of exposure.

 

Posted in Nutrition | 57 Comments

Integrative Veterinary Cancer Care: Are Claims without Evidence Dishonest?

Posted on July 5, 2011 by skeptvet

One of the most frustrating problems with the promotion of alternative medicine and approaches that have not been validated through appropriate scientific testing is that proponents often feel free to make sweeping claims about safety and efficacy despite the
absence of evidence to support these. Personal experience, tradition, or
suggestive pre-clinical research are touted as “proof” of these claims, rather than as the suggestive but poorly reliable bits of evidence they actually are.

Responsible, science-based practitioners are ethically bound to acknowledge the imitations in our knowledge and in the evidence supporting our practices (though being imperfect human beings, of course we may sometimes fall short in this). But practitioners
of alternative approaches can much more aggressively market their practices
beyond the claims justified by good research data, either because they accept
anecdote, intuition, tradition, and personal experience as sufficient evidence,
or sometimes because they disdain the whole epistemological enterprise of mainstream science.

Unfortunately, pet owners and other consumers of veterinary products and services don’t generally evaluate the validity of medical claims from a rigorously evidence-based perspective. In fact, a survey published in the journal Integrative Cancer Therapies, found that scientific evidence was not highly valued by cancer patients investigating
alternative medicine and that anecdotes, information from friends or the Internet, and other sources with low reliability were more highly valued.

Of course, this shouldn’t be surprising. I don’t have the knowledge or expertise to effectively evaluate the competing claims of rival economists, art critics, or automobile mechanics, and we shouldn’t expect every human patient or pet owner to be an expert on
medicine, statistics, epistemology, or the other areas of knowledge and training required to evaluate the evidence and determine the validity of scientific hypotheses and medical claims. That is, after all, our job as doctors. There is a strong ethical duty on the part of doctors to communicate the true state of the evidence for therapies their patients or clients might choose.

However, if we neglect to take this responsibility seriously and accept lower-quality standards of evidence as sufficient, the claims we make are going to be just as persuasive to our clients as those that are actually founded on high-quality scientific evidence.
There is, in fact, a significant advantage to being unconstrained by the limitations and inevitable ambiguities and complexities of scientific evidence when making claims about our treatments. If the only basis needed to claim your interventions work better than anybody else’s is that you believe they do, you are free to say about anything and say it with confidence!

A classic example of this is the blog of a prominent advocate for “integrative” veterinary medicine. This veterinarian makes extensive use of the “bait and switch” approach to
marketing alternative therapies. He advocates many conventional treatments and
then adds unproven “natural” therapies to these. Any positive outcomes are credited to the added natural therapies, rather than the conventional treatment or normal individual variation among patients. However, negative outcomes, such as cancer developing despite the use of natural remedies promoted as protective, are never cited as evidence that the unconventional therapies might not be effective. The whole package is aggressively promoted as superior to conventional therapy, which is denigrated whenever possible. Here is an example:

About 40 years ago, President Nixon declared war on cancer. His goal was to find a cure for this horrible disease. Sadly, we are no closer to reaching that goal today than we
were 40 years ago. In most cases…we really haven’t done a better job of treating or curing cancer. While it is true that survival rates have increased, this is mainly due to early diagnosis. People and pets with Stage 3 or Stage4 metastatic cancer rarely survive.

The situation is no better for our pets. While treatment protocols have changed over the last 40 years, most pets with cancer are expected to only live 6 to 12 months following
diagnosis, and that’s ONLY if owners spend thousands of dollars treating the pet with surgery, radiation, and chemotherapy.

The good news is that using an integrative approach changes these sobering facts and statistics. Designing individualized treatment protocols for each person or pet with cancer,
incorporating a proper diet, nutritional supplements, and other natural therapies offers a much better prognosis for the cancer patient. We now have large volumes of research to show exactly how these natural therapies work in killing cancer and extending the lives of cancer patients.

In my own practice, the average pet with cancer, given a prognosis of 6 to 12 months of life
expectancy from conventional veterinarians, typically lives 12 to 24 months or even longer. Additionally, many pets with “incurable” cancers are cured from their cancers using an integrative approach to boost the pet’s immune system, kill cancer cells, reduce the spread of cancer, and detoxify the patient.

The world of integrative oncology offers much hope for the cancer patient. Integrative
doctors are helping people and pets with cancer live longer lives and in many cases curing cancers that are still considered incurable by conventional medicine.

…After surgery cuts out most of the cancer, and chemotherapy kills most of the cancer, and radiation burns most of the cancer, what’s left to do destroy any remaining
cancer cells? Absolutely nothing! Unless the patient continues therapy, using a combination of proper diet, mind-body medicine, and nutritional supplements, any cancer cells that have survived conventional therapy will, at some point, continue to grow, spread, and ultimately kill the patient.

The sad news is that so many cancer patients will ultimately die after surviving conventional therapies because nothing is done to prevent the recurrence of cancer…not one of these patients is doing anything “natural” to support her immune system or continue the fight against cancer once conventional therapies have finished. How sad and tragic to know that many people will needlessly die out of ignorance once their cancer returns.

…In my own veterinary practice, while I can never offer guarantees to my patients, I tell them that based upon my years of using natural therapies to help pets with cancer, I expect my patients to live one and a half to two times longer than their conventional doctors expect them to live IF they will use properly prescribed natural therapies.

So what are the general messages in this article?

 

1. Conventional medicine has made almost no meaningful progress in cancer treatment in the last 40 years.

2. Conventional therapy is icky (cutting, burning, and killing), expensive, and ultimately not very effective since most pets die of their cancer anyway after less than a year.

3. An “integrative” approach adding “natural” therapies to conventional treatment can
reliably help patients live up to twice as long as those treated conventionally, and can frequently cure cancers when mainstream medicine cannot.

Despite the reference to “large volumes of research” supporting these claims, none is provided in this article. The first claim is obviously and demonstrably untrue. The second consists of an attempt to derogate life-saving therapies by describing them in hostile
language combined with a falsehood. And the third claim is merely opinion with no reliable evidence supporting it.

Clearly, the burden of proving medical claims that are not generally accepted by the medical profession properly falls on the person making the claims. The absence of any effort to support these statements and implications with any evidence beyond personal opinion is a deliberate choice reflecting the author’s lack of interest in careful scientific
demonstration of the value of the therapies he recommends. While I do not intend to do the work of collecting and evaluating the research evidence for this author, I will point out some of the clear factual errors and (deliberate?) misstatements he makes.

1. We haven’t made any significant progress in cancer treatment in 40 years.

This is common claim on the part of those promoting alternative cancer therapies is patently false and has been debunked extensively elsewhere (e.g. A New Perspective on the War on Cancer, which reviews a book on the subject, the Emperor of All Maladies: A Biography of Cancer). Cancer has become a prominent cause of death as people have stopped dying as soon and often from infectious diseases, trauma, malnutrition and many of the other causes of mortality that science and science-based medicine has dramatically reduced. We have a long way to go in figuring out all the factors that contribute to the development of cancer and in preventing and treating cancer. But that is a far cry from saying that we have made no significant progress in the last four decades.

In addition to Acute Lymphocytic Leukemia, which the author acknowledges as an example of a cancer for which we have seen dramatic progress in treatment and patient outcomes, many other childhood cancers are now curable or can be very successfully treated (1). Overall cancer incidence and mortality are falling due to a combination of efforts aimed at prevention, early detection, and improvements in treatment (2). While some cancers have been resistant to the development of effective therapies, others
have seen dramatic increases in the length and quality of life granted by treatment. The National Cancer Institute regularly reports on trends in cancer diagnosis and treatment, and their data clearly shows significant progress since the passage of the National
Cancer Act in 1971.

There is no question the dramatic changes in cancer treatment in the early 20th century have largely been replaced by more incremental and less satisfying small improvements, and we all hope for much greater success in the future. But there clearly has been
significant progress in the last 40 years, and it should be noted that it has
all been due to improvements in science-based, conventional therapy, not so-called alternative medical approaches.

2. “People and pets with Stage 3 or Stage 4 metastatic cancer rarely survive.”

This is one of those statements that is trivially true and also deeply misleading. Of course the most advanced cancer has the shortest life expectancy. The whole point of cancer screening and early treatment is to prevent cancers from progressing to these advanced
stages. The implication for a statement like this is, of course, that by using the author’s methods we could do better. As usual, no evidence is provided to support this assertion.

Since I, like the author of this article, am a general practitioner, I asked a colleague, Dr. Gerald Post, who is a veterinary cancer specialist, to address some of the other specific factual claims made in the article. He was kind enough to share his expertise, and here
is what he has to say:

I usually don’t comment on or disparage my fellow veterinarians, but the claims made by this person were so egregious I could not stop my fingers from pounding on my
keyboard.

Claim A:  “most pets with cancer are expected to liver 6-12 months following diagnosis, and that’s ONLY if owners spend thousands of dollars treating the pet with surgery, radiation, and chemotherapy.” HOGWASH! As a veterinary oncologist, all is see, day in day out is cancer. Many of the cancers that I treat have median survival times of 12 months or longer. We recently published a paper documenting that the survival time for dogs with B cell lymphoma treated with our protocol was over 600 days!!!! Median means that 50% of these dogs lived OVER 600 days.

There are many cancers, such as mammary tumors and many skin tumors that don’t ever see an oncologist—not because they die, but because they are very adequately treated by general practice veterinarians. In many cases these tumors are cured by them and don’t even need an oncologist (and for a veterinary oncologist to say he is not needed is saying a lot).

Claim B: “ In my own practice, the average pet with cancer, given a prognosis of 6 to 12 months of life expectancy from conventional veterinarians, typically lives 12 to 24
months or even longer. Additionally, many pets with “incurable” cancers are cured from their cancers using an integrative approach to boost the pet’s immune system, kill cancer cells, reduce the spread of cancer, and detoxify the patient.”

At the risk of repeating myself HOGWASH!!

Where is the proof for any of these statements? As an ethical doctor, if I were to make any of these statements, I would need to have some evidence –aside from my own beliefs—that
the statements were true. After an exhaustive search of the veterinary medical literature, I was unable to find one reference to support any of the assertions made. Immunotherapy is a very valid treatment, don’t get me wrong. The use of IL-2 in dogs with metastatic cancer is documented. Feline interferon can be used to improve the immune response and increase survival in cats infected with feline leukemia.  These very reputable articles, however, make no claims on curing cancer.

Claim C: ”After surgery cuts out most of the cancer, and chemotherapy kills most of the cancer, and radiation burns most of the cancer, what’s left to do destroy any remaining
cancer cells? Absolutely nothing!”

I am assuming that the author just never heard of metronomic chemotherapy or small molecule inhibitors/tyrosine kinase inhibitors. To make the statement that absolutely
nothing can be done post-chemotherapy, radiation therapy, or surgically is
……you guessed it HOGWASH! Metronomic therapy—the use of very low dose cyclophosphamide, an NSAID, as well as doxycycline, has been shown to decrease
the recurrence rate for soft tissue sarcomas, hemangiosarcomas, and theoretically, because it works by inhibiting the in-growth of new blood vessels—something all tumors need to grow larger than 1-2 mm—it can work on any tumor type.

Please make a note that for the claims I am making, I give you the reader and my clients
information based upon documented and peer-reviewed studies. No one is saying that all studies are absolutely factual or that future studies will not refute some claims made by earlier studies. But I am saying that basing my recommendations and claims on evidence IS important. As a reader and as a client you deserve it. When you see a doctor you are relying not only on his or her expertise, but also on the combined knowledge of all the
clinician/scientists in the world!

At the end of the day, the reason why evidence is important is respect! Respect for my clients, respect for my patients and respect for my profession. I truly believe that
those people who seek out cancer treatment for their pets love their pets dearly and are intelligent people, who deserve the best information possible. This empowers them so that they can ultimately make the wisest decision for themselves.

3. Adding “natural remedies” to conventional cancer treatment can prolong life and even cure cancers conventional treatment alone cannot.

This is the core advertising message in the article, and there is not a speck of evidence to show it is true. Substituting alternative medicine for conventional cancer treatment is almost always harmful, as the sad outcome of the NCCAM-funded study of the Gonzalez cancer therapy for pancreatic cancer and many individual anecdotes illustrate. As for adding unproven therapies to conventional treatment, there have been numerous pre-clinical studies and small, low-quality clinical trials published investigating specific alternative therapies used in this way. A few positive results have been reported here and there,, but there is certainly no clear and persuasive body of evidence to show that such an
approach improves quality of life, survival, or any other meaningful, measurable outcome of cancer treatment. This claim is pure ideology and advertising unsupported by solid science. As such, it is at least deeply unethical and at worst false advertising.

Bottom Line

The claims made in this article disparaging scientific cancer therapy and lauding the benefits of adding unproven alternative methods to conventional treatment are unsupported by reliable scientific evidence. Science has made significant progress in
preventing, detecting, and treating cancer and undoubtedly will continue to do
so. This progress has been, and will continue to be due to rigorous, systematic
scientific research. A reliance on tradition, anecdote, personal clinical
experience, and low-quality scientific evidence to justify cancer therapies is
not in the best interest on cancer patients. The good news is that scientific medicine offers real hope for continued improvement in the length and quality of life for cancer patients. The bad news is that some of these patients will be denied the full benefits of scientific medicine and subjected to unnecessary, unhelpful, and sometimes even harmful alternatives if they are misled by sweeping and confident claims unsupported by real evidence. It is our responsibility as doctors to ensure our patients and clients have the full and true facts about their options so they can choose the best possible care for
themselves and their pets.

Posted in General | 12 Comments

Dietary Carbohydrates and Cats: It’s the Calories!

Posted on June 22, 2011 by skeptvet

One of the most common questions regarding veterinary nutrition that I get from clients these days is about cats and grains. An argument often made about feline nutrition is that because they are obligate carnivores, cats are ill-equipped to eat carbohydrates and that since commercial diets often include grains and other carbohydrate sources, these must be nutritionally inappropriate for cats. This argument is especially tricky because it is partially correct and partially a fallacy. It is true that cats are obligate carnivores, and diets that exclude all animal products are nearly impossible to make so that they will meet cats’ nutritional needs. On the other hand, there is a significant difference between nutrients in a diet and the ingredients in the diet. Proteins and carbohydrates derived from plant sources can be just as digestible and nutritious for cats as those derived from animal sources. The devil is in the details, and it is usually unwise and inaccurate to make sweeping generalizations about pet nutrition.

A panel of nutrition and feline medicine experts from the American College of Veterinary Medicine (ACVIM) recently drafted a consensus statement on the role of dietary carbohydrates in feline obesity and diabetes which examines some of the evidence concerning dietary carbohydrates and cats. This statement clarifies some questions but also leaves room for debate because it is based not on pure theory and argument but on research evidence, and there are areas in which the research evidence is inconclusive. This sort of ambiguity can be quite frustrating, but it is better to acknowledge the limits of our understanding and work towards expanding them than to simply take the lack of definitive information as an excuse to accept and promote whatever theoretical argument most appeals to us.

The statement was presented at the recent ACVIM annual meeting in the form of a series of questions about dietary carbohydrates in feline diets with brief answers and then an assessment of the strength of the evidence supporting these answers. The statement itself should be published soon, and will doubtless instigate vigorous debate, as it should. I will post a link to the statement and updates as they become available. But for now, here is a summary of the statement as presented at the recent conference.

1. Are dietary carbohydrates an essential or required nutrient for cats?
Answer- No. Based on a good quality and quantity of evidence, most cats do not require dietary carbohydrates. There are some simple sugars in feline milk, so it is possible that nursing kittens may require these but no clear deficiency has been demonstrated.

2. Can cats effectively utilize dietary carbohydrates for energy and nutrition?
Answer- Yes. Based on a good quality and quantity of evidence, cats can effectively digest, absorb, and utilize dietary carbohydrates.

3. Do dietary carbohydrates in the diet cause obesity?
Answer- No. The cause of obesity in almost all cats is excessive calorie intake irrespective of whether the calories come from protein, fat, or carbohydrate. In fact, low carbohydrate foods may be more likely to lead to obesity if they are higher in fat than regular diets.

4. Do dietary carbohydrates contribute to the development of diabetes?
Answer- The consensus was that they do not, however the research evidence is very limited and not always consistent. The consensus was that even if carbohydrates do play a role as a risk factor for diabetes, this is dwarfed by the much more important factor of obesity.

5. Are low-carbohydrate diets useful in the management of feline diabetes?
Answer-Maybe. The evidence is limited and conflicting, and the committee did not achieve a consensus.

The lead presenter summarized the central finding of the panel with three words:

“It’s the calories, Stupid!”

Posted in Nutrition | 7 Comments

From Bloodletting to Evidence-Based Medicine by Dr. Brad Hanna

Posted on June 18, 2011 by skeptvet

This is a clear and compelling description of how “Traditional Western Medicine” developed and functioned exactly as much alternative medicine does today, on the basis of tradition and anecdote, and how it was abandoned in favor of scientific medicine. Dr. Hanna illustrates as clearly as I have ever seen why science-based medicine is more reliable than folk medicine, and why it has largely supplanted folk practices wherever there are sufficient resources to make this possible. Bravo Dr. Hanna!

From Bloodletting to Evidence-Based Medicine

Posted in General, Science-Based Veterinary Medicine | Leave a comment