Artemisinin-Is It a Useful Drug for Cancer Treatment in Dogs?

Posted on August 12, 2014 by skeptvet

A couple of readers have asked about a purported cancer therapy agent called artemisinin. This is a compound derived from a plant and used for a variety of purposes in the system known as Traditional Chinese Medicine. It is sometimes recommended outside of this system as an herbal therapy for cancer, with the usual claims of dramatic benefits and virtually no risk of side effects. As we’ll see, the truth is more complex and more interesting than such simplistic claims.

What Is It?
A number of compounds have been identified in the plan known most commonly as Sweet Wormwood. Artemisinin is the most widely studied of these and the one most often claimed to have medicinal benefits. The usual forms in which the drug is given is as a dried herb or infusion (steeping the plant in water like tea).

It has been claimed to have benefits in treating cancer and fungal or parasitic infections in pets. It is also widely used, in conjunction with other drugs, in treatment of malaria in humans.

Does It Work?
There is no question that artemisinin has been useful in the treatment of malaria. Like any effective medicine, of course, it has been shown to have side effects (relatively low rates of nausea and vomiting, rare allergic reactions and possibly liver damage), and there is now evidence that malaria is developing resistance to artemisinin-based therapy.

The evidence for use in cancer therapy is not nearly as convincing (see also this review). There are a number of in vitro and lab animal studies showing potentially useful effects on cancer cells. However, this has been true for most cancer therapies that have gone on to be failures in actual clinical trials, so all it establishes is the possibility the drug might be useful, not that it actually is.

The next level of evidence is the case report, which is simply a formalized, published version of the anecdote. There are some case reports showing improvement in human cancer patients with use of artemisinin and related compounds (e.g. 1, 2). However, as with all anecdotes, these reports are subject to enormous risk of bias and confounding, and it is not appropriate to draw conclusions about the safety and efficacy of artemisinin from them. At most, they suggest the possibility that further, controlled testing is appropriate.

There isn’t much in the way of such evidence in humans. One clinical trial combining the compound with chemotherapy for lung cancer patients found no difference in terms of short, medium, or long-term survival. Some difference was seen in the rate of disease progression, but the reality and clinical relevance of this is doubtful, and the source is pretty questionable since it is a Chinese alternative medicine journal, and such journals appear to never publish negative results.

There is, similarly, virtually no clinical trial literature in veterinary species evaluating artemisinin as a cancer therapy. A clinical trial investigating the related compound artesunate as a therapy for lymphoma in dogs has recently been published:

J.N. Bryan, D. Tate, S.M. Bechtel, K. Choy, L. Donnelly, K. Fitzpatrick, B.K. Flesner, B. Fowler, B. Gallis, C.J. Henry, C. Herrera, M. Jabbes, K.A. Selting, T. Sasaki. Randomized, blinded, placebo-controlled trial of artesunate with doxorubicin for B-cell lymphoma of dogs. J Vet Int Med. 2014;28(4):1362.

Artemisinin has described anti-cancer properties. Artemisinin can down-regulate VEGF, HIF-1alpha, and survivin in cancer cells, causing apoptotic death. Artesunate, a water-soluble derivative, has better oral absorption in dogs than artemisinin. The hypothesis was that oral artesunate is tolerable with doxorubicin and results in longer disease-free interval (DFI) than doxorubicin and placebo in dogs with stage 3a or 4a B-cell lymphoma.

Twenty-one qualifying dogs were randomized (blinded) to receive artesunate 20 mg/kg or equivalent placebo. Dogs received study drug alone for 72 hours, then received 30 mg/kg doxorubicin q.3 weeks for three doses with study drug. Thereafter, lymph node measurement, CBC, chemistry profile, and urinalysis were monitored monthly until disease progression. Differences and DFI were compared by Mann-Whitney and Kaplan-Meier logrank tests. Significance was set at P ? 0.05.

Artesunate alone did not cause clinical remission (P = 0.1347). Artesunate induced no biochemical toxicosis. One dog experienced progressive disease following doxorubicin; all others experienced a complete response. Artesunate caused no greater neutropenia or thrombocytopenia following doxorubicin (P = 0.6234 and P = 0.2311). DFI was not different between groups (70d for placebo and 122d for artesunate, P = 0.967). Dogs receiving artesunate had higher nucleated red blood cell counts (median 272nRBC/100WBC artesunate and 9nRBC/ 100WBC placebo, P = 0.0142). Red cells displayed poikilocytosis and basophilic stippling in artesunate-treated dogs.

Artesunate did not cause remission as a single agent, nor improved DFI in dogs treated with doxorubicin. 20 mg/kg artesunate caused evidence of heme stress in treated dogs. Artesunate was otherwise well tolerated with doxorubicin. Artesunate cannotbe recommended as a therapy for B-cell lymphoma in dogs.

This trial, like that reported in humans, found no evidence that artesunate improved survival used in conjunction with chemotherapy, and it did not appear to have any beneficial effects used alone.

Another uncontrolled clinical trial in dogs was identified some possible toxicity as well as some possible benefits, but was the heterogeneity of patients and treatments make any firm conclusions impossible.

So far, the clinical trial evidence does not strongly support the preliminary in vitro and lab animal studies or case reports that suggested these compounds might have benefits in cancer patients. This is not unusual, since the vast majority of drugs fail to become useful treatments in actual patients even when they initially look promising in pre-clinical studies. More research may help clarify the value, if any, of artemisinin in cancer therapy.

Is It Safe?
A number of potential risks to artemisinin have been reported in humans and other species. Generally, side effects have been mild and rare in humans, with low rates of vomiting and other GI symptoms reported. There have been concerns about neurologic toxicity, including hearing damage, but it is not yet clear how significant this risk really is. In the context of malaria treatment, where there are clear benefits, the risks appear to be small enough in most cases (other than pregnant women and, possibly, young children) to justify use. However, the risks in cancer patients have not been established.

In dogs, there have not been safety studies in cancer patients either, however there is stronger evidence of risk with artemisinin use. One study of various forms and routes of administration found anemia, neurotoxicity, and changes in mitochondria. Other studies have also found significant toxicity at high doses (see also this study). However, other studies using different forms and dosages have not reported adverse effects.

Bottom Line
There is clear clinical trial evidence that artemisinin is useful in the management of malaria in humans, though there are some concerns about it losing its efficacy. Side effects are reported, but they are usually mild and uncommon.

There is some pre-clinical evidence (in vitro studies and lab animal studies) suggesting artemisinin and related compounds might have some benefit in cancer treatment. This is supported by a few uncontrolled case reports in humans. However, the limited clinical trial evidence does not generally support any real benefit for actual patients, human or canine. More research is needed to clarify whether there are circumstances in which the drug might be helpful, but it is by no means a reliable, proven cancer therapy.

Pre-clinical trials in dogs have found some potentially significant risks, which seem to be greater than those seen in humans. Some of these, such as changes in red blood cell production, have also been seen in the limited clinical trials done in dogs, but others have not.

Overall, there is enough evidence to support further controlled clinical research but not to use the treatment in patients outside the context of appropriate clinical trials designed to assess safety and efficacy.

Posted in Herbs and Supplements | 73 Comments

Routine Vaccinations for Dogs & Cats: Trying to Make Evidence-based Decisions

Posted on August 5, 2014 by skeptvet

Introduction
As part of my effort to practice medicine based solidly in scientific evidence, I regularly review my own practices and recommendations and make adjustments as seems indicated by new evidence. The quantity and quality of scientific research in veterinary medicine is often less than ideal, so absolute right or wrong answers are seldom clear. But over time changes in the available evidence sometimes justify changes in practice. One area in which this has been particularly true in the more than 15 years since I started in vet school is the subject of vaccinations for dogs and cats.

Unfortunately, the vaccination issue is all too often taken out of the realm of rational, science-based discussion and made part of ideological battles over different approaches to medicine that have little to do with a sound assessment of the risks and benefits of vaccines. This is unfortunate and unnecessary, but given the politicized nature of this topic, I will begin by stating my basic perspective before getting into the details.

I believe vaccines are one of the most successful and beneficial healthcare interventions ever developed. Like any real medicine, vaccines have risks as well as benefits, but history is unequivocal that vaccines have saved and improved the lives of humans and animals to a degree that dramatically overshadows any harm they have done. Most of the opposition to vaccination in the last decade, for children as well as for pets, has been irrational, unscientific, and pretty thoroughly baseless. The kinds of dangerously misguided and misinformed anti-vaccine positions of all too many proponents of alternative medicine are not based in science and represent a serious threat to the health of our pets.

With all of that said, the mainstream veterinary approach to vaccination has often not been soundly based in science either. Habit, inertia, and economic considerations have led some vets to ignore growing scientific evidence and continue giving some vaccines more frequently than necessary. The latest data I have been able to find, which is from 2006, suggests up to a third of small animal vets give certain core vaccines more often than is recommended (I’ll get into the details in a bit). This is far fewer than the majority sometimes claimed by critics of science-based medicine, but it is still an illustration of the resistance to change in routine practices even when good evidence supports the change.

So what does the evidence say about vaccinations for dogs and cats? What should they be vaccinated for? With which vaccines? How often? Not surprisingly, these are complicated questions with complicated, nuanced answers. Simple, one-size-fits-all rules may be convenient, but they don’t reflect the complex nature of biology. The best review so far of vaccination research concerning dogs is the 2011 American Animal Hospital Association Guidelines on Canine Vaccinations. For cats, the 2013 American Association of Feline Practitioners Vaccination Advisory Panel Report is a useful document. Both of these are consensus statements issued by a limited group of experts, and they don’t meet the standards of a fully transparent, systematic review of the evidence. But they do provide a good summary of existing research and a reasonable interpretation of the how the research might translate in vaccination practices.

Vaccination, like any medical therapy, needs to address the specific needs of the individual patient. One cannot make a decision about which diseases to vaccinate against until one has some understanding of which diseases a patient is at risk of getting. This involves considerations such as age, exposure to other animals, general health, and so on. Unfortunately, the specific risk of a particular disease in a given setting is not always known since there are no regular, systematic or comprehensive surveys of how common most cat and dog diseases are everywhere in the country. However, some general guidelines and the experience of practitioners in a given area can help give a crude idea of whether a particular patient is likely to be at risk for a particular disease and to benefit from vaccination for it.

Dogs
The AAHA guidelines for dogs categorizes vaccines as core, those that are most likely to be widely beneficial, because the diseases they protect against are common, and non-core, those which are only appropriate for dogs with specific know risk factors for a particular disease. The guidelines also assess the general efficacy and safety of particular vaccines and the available information on duration of protection, which helps us decide how often to repeat particular vaccines.

Based on this information, most puppies should have a series of vaccinations for canine distemper and parvovirus every 3-4 weeks from about 6 weeks of age to 16-18 weeks of age, one rabies vaccination after 12 weeks of age and boosters for these one year after the last in the puppy series.

Duration of protection is at least 3 years for most licensed canine rabies vaccines, and they are legally required in most places every three years for life. From a medical point of view, a reasonable argument can be made for less frequent rabies vaccination or for alternatives, such as monitoring antibody titers. But in most cases these alternatives are not legally permitted. This is a function of the fact that rabies is widely present in wildlife and nearly 100% fatal for humans (and all other mammals) who catch it, so the public health authorities choose to err on the side of caution when using vaccines to prevent transmission from dogs to humans.

Some research efforts are under way to try and support changes in these laws, so these rules may be altered at some point. However, it is important to remember that while the evidence suggests less frequent vaccination for rabies might be effective in protecting dogs (and humans), it also suggests that the current guidelines of revaccination every three years is safe and very, very unlikely to harm most dogs. While I would welcome an evidence-based change in the rules regarding rabies vaccination intervals, I do not think there are risks that justify defying the rules in the meantime.

For distemper and parvovirus, the other core vaccines, there is strong evidence that protection for most dogs lasts at least 5 years, and pretty good evidence for longer duration of immunity. The guidelines recommend repeating vaccination no more than every 3 years, and 3 years is the interval most commonly used today. However, longer intervals are probably justified. There is certainly no need for annual boosters, and this is a practice that really isn’t defensible scientifically.

Antibody titers can be useful in some cases, since a high titer does indicate a dog is protected and does not require additional vaccination. However, a low titer does not necessarily mean a dog is susceptible, so it is less useful in trying to decide when to revaccinate.

Given the length of protection, and some evidence that susceptibility to parvovirus is low in older dogs, most probably do not need to be vaccinated after about 8-10 years of age. There is clear evidence that older dogs do respond appropriately to vaccinations, and there is not evidence that they are more likely to be harmed by vaccines than younger dogs, so continuing to vaccinate after this age is not likely to be harmful, but it is probably unnecessary. In humans, there is evidence that older people may be more susceptible to some diseases than younger adults, and thus may be more in need of vaccination, but this hasn’t yet been demonstrated in dogs.

Given the degree of safety for most of these vaccines, if there is significant uncertainty about whether a given dog is protected or has had appropriate vaccination for these diseases, giving the vaccine is safer than not giving it.

The AAHA guidelines cover in detail many of the other available vaccines. Most are not regularly recommended, usually because the diseases they protect against are mild or uncommon or because the vaccines are of poor or uncertain effectiveness. Some are quite controversial, such as that for Lyme Disease. Most are only appropriate for dogs with particular risk factors, not for routine use on all dogs.

Cats
The AAFP guidelines for cats are similar to the AAHA canine recommendations, identifying core and non-core vaccines and providing general guidelines for use of these as well as suggestions for how to develop individualized vaccination recommendations. Most cats should have a series of vaccines for feline herpes virus (FHV) and calicivirus (FCV) and panleukopenia (FPV) between 6 and 20 weeks of age and boosters for this one year later. Thereafter, 3-year intervals are recommended for life, though there are a variety of factors that may alter this plan.

Feline leukemia vaccination is also recommended for most cats. While many indoor only cats may not be exposed to this disease, the recommendation is for all cats to have an initial vaccine and one year booster because it is not always possible to predict future lifestyle or exposure status for kittens. Boosters are recommended every 1-2 years depending on risk of exposure. Recommendations for other vaccines depend on the needs of individual cats. Other vaccines are assessed on a case-by-case basis.

In general, I recommend following these guidelines for the initial vaccine series and the one year booster. I often cease vaccination for strictly indoor cats after that, however this involves a thorough discussion of the possible risks. If a cat escapes every once in a while, for example, they should certainly be kept current on rabies vaccination. And, of course, if there are legal requirements for rabies vaccination, these should be followed. Cats that visit other cats or have visitors or new cats come into the household, cats who attend shows or are boarded, and cats with owners who interact with cats outside the household may benefit from vaccination even if they are strictly indoors.

The risks of vaccination are generally similar in cats as in dogs, and very small, with one significant exception. The evidence is stronger for the development of a very serious kind of cancer, called a sarcoma, associated with some vaccines in some cats. The risk of this is still very low (reported to occur following as few as 1/10,000 doses of vaccine to as high as 36/10,000 doses), but it is a very dangerous and often fatal disease. Changes have been made in the vaccine used in cats to try and reduce this risk, but it isn’t absolutely clear if these changes have lowered the risk. This disease needs to be considered when making vaccination decisions for individual cats, and certainly we need to make a serious effort to avoid unnecessary vaccination. However, irrational fear of this disease is not a good reason to subject cats to unnecessary risk from equally serious infectious diseases by avoiding appropriate vaccinations.

Conclusions
Because the scientific evidence is never perfect or complete, it is not unusual for different individuals to have different interpretations of it, and more than one of these may well be reasonable and appropriate. For example, I tend to recommend distemper and parvo boosters every five years, but there is nothing wrong with recommending these every three years.

On the other hand, the evidence is often sufficient to make some interpretation unreasonable. Annual boosters for these vaccines are almost never justified, and complete avoidance of them, or refusal to vaccinate adult dogs is not sound medical practice. The evidence may not always provide a single right answer, but it can help establish a range of reasonable options from which to choose.

My own vaccination practices have changed significantly during my career as a result of both changes in the evidence and new assessments of existing studies. The practice of evidence-based medicine requires regular re-assessment of the interventions we offer. Unlike in some domains, such as politics, changing one’s mind in science is understood to be a good sign, and indication that a good clinician is committed to providing the best science-based care possible. I always emphasize in this blog that our patients and clients deserve the best care, and that care is going to be treatments for which we have as much scientific evidence as possible to understand the real risks and benefits.

This applies to all veterinary interventions, conventional as well as alternative. I tend to focus on alternative therapies here partly because there is so little skeptical, critical information about them available to help pet owners make informed decisions and also because, frankly, they are quite often far less founded in science-based theory and evidence than conventional approaches. However, the same scientific standards of evidence should apply to all treatments regardless of their provenance. Accepted conventional practices need to be scrutinized as closely as alternative therapies. When there is some uncertainty about the evidence, I endeavor to apply this scrutiny just as I do for unconventional treatments. My articles concerning neutering, cruciate ligament disease, and stem cell therapy, in addition to this and previous discussions of vaccination, are examples of this.

Since my position on vaccines tends to be very similar to that of many proponents of alternative therapies, I thought it would be useful to discuss it explicitly here. There is a tendency to caricature and demonize those with whom we disagree on issues we feel strongly about. It is often assumed, for example, that I blindly give all dogs annual vaccinations because this is a stereotype image of veterinarians who are critical of alternative therapies. But of course a science-based evaluation of an intervention like vaccination can and should be every bit as thoughtful and focused on the needs of the individual and the risks and benefits of the intervention as alternative practitioners claim they are. I believe the science does not support annual boosters for core canine vaccines, so I no longer recommend them.

Similarly, it is tempting to assume all proponents of alternative therapies hold the most extreme anti-vaccine views espoused by members of their community, but that is likely inaccurate and unfair also. I see no reason to shy away from points of agreement with folks on some issues even when one has serious disagreement with them on others. Hopefully, such points of agreement might even act as bridges to allow more realistic and respectful communication and disagreement, though my experiences in this area haven’t led me to be very optimistic about that.

In any case, it happens that I often agree with the criticism of vaccination practices put forward by proponents of alternative medicine, if not always on the basis of the same reasoning or evidence. This will likely neither tarnish my credibility with skeptics nor improve it with proponents of alternative medicine, but hopefully it will illustrate that I am committed to following the evidence over ideology as best I can.

Posted in Vaccines | 69 Comments

Ocu-Glo Rx: A Nutritional Supplement Marketed to Support Eye Health and Vision

Posted on July 27, 2014 by skeptvet

A reader recently asked me to comment on a dietary supplement marketed for dogs and cats, Ocu-Glo Rx. While this product shares the problem of many such supplements,  a shaky theoretical rationale and limited relevant research evidence to support its use, I was pleasantly surprised to find that at least the claims made by the company are fairly circumspect and reasonable compared to many similar products. The founders of the company are board-certified veterinary ophthalmologists with legitimate and relevant training and research experience, and they seem to have approached the design and marketing of this product a bit more scientifically than is commonly the case.

What is It?
The company that makes this supplement is pretty clear and specific about the ingredients, which is unusual compared to many veterinary supplements.

Grapeseed Extract
Lutein/Zeaxanthin
Omega-3-Fatty Acids
Vitamin C
Vitamin E
Lycopene
Zinc
Epigallocatechin Gallate (Green Tea Extract)
Alpha Lipoic Acid
Vitamin B Blend
CoEnzymeQ10

The site even lists the specific amount of each ingredient in the two sizes of capsule.

The claims made for the product are also refreshingly reasonable compared to many such nutraceuticals. In keeping with the requirements of the minimal regulations governing dietary supplements, the product is marketed as “supporting” the normal function and health of the eye: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.” Claims for preventing or curing disease would be inappropriate and illegal. Though some of the testimonials and marketing seem to imply more than a purely supportive nutritional role for the product, the web site is pretty good about sticking to allowable claims.

Ocu-GLO Rx™ is needed when your dog is showing any of the following signs:

– Diminished vision at night or in dim conditions – Diminished vision at all times – Cloudy appearance to eyes – Pupils that do not constrict – Obvious cataracts Or… -Your dog is generally healthy, but you want him or her to be placed on an excellent lifetime antioxidant supplement to help support and enhance ocular health and also general health.

We (Drs. Carmen Colitz and Terri McCalla) are also dispensing Ocu-GLO Rx™ for patients predisposed to primary glaucoma (having lost their first eye to glaucoma) and that already have glaucoma; for Golden Retrievers with pigmentary uveitis (also called “Golden Retriever Uveitis” or GRU); for diabetic dogs in which cataracts are immature or have not yet formed; for dogs with senile retinal degeneration; for dogs post-cataract surgery to help reduce the incidence of PCO and ACO (Posterior Capsular Opacity and Anterior Capsular Opacity) and for any dogs for which owners want to provide the best nutritional support for their pet’s eyes.

Please keep in mind, however, that the goal of giving Ocu-GLO Rx™ to your dog is not to cure anything—it is to help lessen ocular damage caused by disease and hopefully “buy some time” in which your dog still has functional vision.

It is very important to understand that for many canine eye diseases, medication and/or surgery might be needed in addition to giving your dog Ocu-GLO Rx™.

Please also know that for dogs that are already completely blind from any of these ocular diseases (especially PRA, SARDs, cataracts, GRU, or glaucoma), it is very unlikely that Ocu-GLO Rx™ will be of significant benefit. As a general rule, Ocu-GLO Rx™ can help to prevent or slow down progression of some ocular diseases but cannot reverse ocular damage that has already occurred. For example– Ocu-GLO Rx™ cannot reverse cataracts.

[emphasis added]

Does It Work?
The theory behind the product is predominantly a version of the antioxidant hypothesis, the claim that chronic diseases can be partially attributed to free radical damage to tissues or DNA and that these diseases can be prevented or ameliorated by nutritional supplementation with anti-oxidants. This was once a wildly popular idea, but in the last ten years it has taken quite a beating, and generally antioxidant supplements have failed to fulfill their promise in the prevention of most disease for which it was hoped they would be useful. While epidemiologic evidence supports a diet rich in foods containing antioxidants, the use of dietary supplements does not seem nearly as beneficial in most cases.

With specific regard to diseases of the eye, the evidence for benefits from antioxidant supplements in humans is mixed. Systematic reviews do not seem to show a benefit in terms of preventing cataracts (1) or macular degeneration (2, 3, though some positive trials do exists and others are in progress), and the evidence is not strong for other eye diseases. Of course, “Do antioxidants prevent eye disease?” is another of those unanswerably vague questions. The more useful questions would focus on specific compounds for specific diseases in particular populations. Many more specific studies on such focused questions could reasonably be conducted, and it is certainly not unreasonable to hope that some would show beneficial effects.

As usual, there is virtually no relevant clinical research in dogs or cats, so even the inconsistent and preliminary evidence for such products in humans is not available to us for our pets and patients. The company web site does cite a number of scientific studies to support the inclusion of each ingredient in the product, however, these are generally lab animal studies or human studies, not clinical trials investigating the preventative effects of the product or the ingredients for specific diseases, so extrapolation to clinical use in dogs and cats should be tentative at best.

Is It Safe?
For a long time, one pillar of the antioxidant hypothesis seemed to be that antioxidants were necessarily safe since they occur in foods. That has since been clearly shown to be untrue, and there is ample evidence that supplementation can have risks as well as benefits. The benefits of any compound that affects physiology are going to have parallel risks, and the importance of good scientific studies lies largely in helping us to understand these risks and benefits so we can make decisions about the balance between them in specific situations.

While reasonable amounts of nutrients commonly found in foods are unlikely to have dramatic risks, the true safety of these kinds of supplements cannot be known without appropriate research. The product web site indicates that some sort of safety study has been conducted, but I have not been able to find any indication that it has been published, so it isn’t possible to evaluate the reliability of that evidence.

Bottom Line
The theoretical rationale behind the selection of ingredients in this product is certainly plausible, and there is some evidence in humans and lab animals to suggest some of them might have beneficial properties. However, the theory of oxidative damage has mostly failed to bear real-world fruit in terms of supplements validated as effective in clinical trials. The human clinical trial evidence for the ingredients in this product varies from weakly positive to mostly negative to insufficient to draw conclusions. There is no published clinical trial evidence in dogs and cats to support the safety or efficacy of this product for preventing or treating any eye disease.

It is unlikely that there are significant risks to using this product, though studies in humans have found dangers to antioxidant supplementation when enough people were studied for long enough, so it is not possible to confidently claim there are no meaningful risks.

Unlike the marketing for many supplements pitched to pet owners, the claims made by this company are pretty measured and reasonable in light of the limited available evidence (though the company has unfortunately been unable to avoid the allure of the meaningless feel-good term “natural” in its marketing). It is debatable whether the evidence is sufficient to justify marketing a product like this at all, but at least the manufacturer is avoiding wild and exaggerated claims. Hopefully, the ophthalmologists behind the product will pursue appropriate research efforts to determine if, in fact, the product has the benefits they suspect and what, if any, risks are associated with its use.

Posted in Herbs and Supplements | 52 Comments

Potential Risks of Neutering and Age at Neutering for Golden Retrievers and Labrador Retrievers

Posted on July 17, 2014 by skeptvet

A number of interesting and important research studies have been published in the last 5 years on the subject of the risks and benefits of neutering in dogs, and these have provided important information to help guide veterinarians and owners in making decisions about neutering. I published a narrative review of the literature on neutering in 2010, before most of these papers appeared, and I have been following this area of study with interest and evaluating individual papers as they are published. Though each study has its limitations, as is always true in science, and we must be careful not to overgeneralize the results of particular studies or lurch wildly from one set of recommendations to another on the basis of limited evidence, these studies are influencing traditional dogma about neutering. I have made several significant changes in both the information I give to owners and the recommendations I make about neutering based on the emerging evidence.

Another important study has recently been published which adds to the evidence in this area.

Hart BL, Hart LA, Thigpen AP, Willits NH. Long-Term Health Effects of Neutering Dogs: Comparison of Labrador Retrievers with Golden Retrievers. PLoS ONE 2014;9(7): e102241. doi:10.1371/journal.pone.0102241

This study was produced by the same group which published an earlier retrospective study of Golden retrievers, and it is quite similar in its methods and some of its limitations. The authors reviewed medical records from the veterinary hospital at the University of California Davis veterinary college. The study looked for Golden retrievers and Labrador retrievers from 1 to 8 years of age and evaluated the occurrence of 6 diseases relative to neutering status and age at neutering.

The findings are summarized in Table 1 for Labradors and Table 2 for Golden retrievers. For comparison, I have also extracted similar data from the earlier paper by on Golden retrievers by the same group in Table 3. This paper classified age at neutering differently (early being <12 months of age and late being >12 months of age), so the studies are not directly comparable, but it is useful to scan for any possible patterns that might help us make sense of these complex data.

First off, what does the study appear to show? Well, perhaps the most important finding is that there are significant differences in the pattern of possible effects of neutering between males and females, and also between the breeds. This latter point is extremely important. People tend to jump on the findings from a study in a single breed and want to generalize those findings to all dogs and make broad recommendations based on that single study. However, if the possible effects of neutering differ significantly between two breeds as closely related and similar as Golden retrievers and Labrador retrievers, likely these effects will be even more dissimilar in breeds less closely related. A study of Rottweilers or Viszlas, for example, may tell us little or nothing about what to expect in Beagles or Poodles. This is worth keeping in mind before we rush into making sweeping recommendations for all dogs.

The findings in this study suggest some increase in the risk of some diseases with neutering, but the patterns were not very consistent. Neutering before 6 months of age appeared to be associated with higher risk of cruciate ligament disease and elbow dysplasia in male Labradors but not with the risk of hip dysplasia. In females, however, the pattern was the opposite, with neutering at less than 6 months being associated with greater risk of hip dysplasia but not the other two orthopedic diseases. But in Golden retrievers, neutering before 6 months of age was associated with greater risk of cruciate ligament disease in both sexes, but with greater risk of hip dysplasia only in males, not females.

Comparing the current study with the previous study of Golden retrievers also adds to the confusion. In the current study, risk of lymphoma seems to be higher in dogs neutered between 6-11 months than in intact dogs, but not in dogs neutered before 6 months or after 11 months. In the previous study, however, lymphoma risk appeared higher in males neutered before 12 months but not in females neutered at this age. In another example, late neutering in the first paper seemed to increase the risk of hemangiosarcoma in female Goldens but not in males. This was contrary to the hypothesis that earlier neutering might increase the risk of this cancer. However, in the current study, no differences in hemangiosarcoma risk were found for any neutered group of males or females compared to intact dogs.

There are, as always, a number of limitations that we must bear in mind when evaluating this study. As with the previous study, dogs were those seen at a university veterinary hospital. This is a very different population than usually seen at regular general veterinary practices. The veterinary hospital at UC Davis typically sees seen sicker dogs, dogs with more affluent owners, and dogs that live in different areas than those seen by regular practices in the rest of California. So we have to be careful about assuming than any relationships seen between health and neutering in this population will hold for the very different population of primary care practice patients.

Dogs younger than 12 months were excluded from this study. While the disease looked at are less common in dogs less than 1 year of age than in older dogs, they do occur. If dogs who get these diseases under 12 months are different, in terms of neuter status, from the dogs looked at in this study, that might change the apparent relationship. For example, if dogs who are intact are more likely to get one of these diseases earlier than neutered dogs, then excluding younger dogs would make neutering seem like a risk when it might actually be protective.

Similarly, dogs over 9 years of age were excluded as well. These dogs are particularly likely to get some of the cancers looked at in the study, and again if the ones who do differ in neuter status from the ones in this study, the apparent relationships identified in the study might be very different from the real relationships between these diseases and neutering.

A number of potential benefits of neutering, such as preventing mammary tumors and uterine infections in females and possibly being associated with longer overall lifespans, were not included in this study. While these are not directly related to the questions the authors sought to investigate, it is important that we consider overall risks and benefits when deciding when or if to neuter our dogs. If neutering prevents some cancers and increases the risk of others, for example, we need to make a decision about which effect is greater or more important in a particular dog. This study only looks at a small piece of that equation, namely the risks but not the benefits.

Finally, there are many comparisons made in this study, and each one is evaluated statistically. This can create a problem known as the multiple comparisons problems, in which the usual threshold for statistical significance is not appropriate. It is common, in studies which make multiple comparisons between subgroups and don’t correct for this problem to find a smattering of statistically significant results which are really the result of chance. In this study, I am not certain if a correction for multiple comparisons was made. If not, this could explain some of the significant differences found, particularly when the overall pattern is not consistent between studies or does not fit expectations based on biology.

Bottom Line
Overall, this study does suggest that neutering under 6-12 months of age might be associated with an increased risk of some orthopedic diseases in Golden retrivers and Labrador retrievers. In Labs, neutering does not appear to increase cancer risk. In Goldens, there may be some effect on cancer risk, but it differs between males and females. And in females, it may even be the case that earlier neutering is associated with a lower cancer risk than neutering later in life. But there are a number of inconsistencies and limitations which make these findings tentative at best.

The study also appears to show a strong difference in the effects of neutering on disease risk between even very closely related breeds. So it is important to recognize that the effects seen in one breed cannot reliably predict those that might be seen in another.

No single, universal recommendation for neutering or not neutering dogs of any sex, breed, or age is justified by the scientific evidence. There is some suggestion that females may experience significant health benefits, particularly in prevention of pyometra and mammary tumors, though the evidence concerning mammary tumors is weaker than generally believed. For males, there does not seem to be a compelling, consistent health benefit to neutering, and in large breeds there may be some benefit to waiting until after 1 year of age. In any case, as I always stress, it is important to balance potential risks and benefits carefully.

And not all benefits of neutering are related to the health of the individual dog. Millions of unwanted dogs are born and euthanized in the U.S. every year, and while every client I talk to dismisses the possibility that their dog could contribute to that problem if left intact, most of these dogs are the product of breeding by owned pets. So if you choose to keep your dog intact for health reasons, it is important to accept that this creates an additional responsibility to make sure he or she does not contribute to the serious problem of overpopulation and the suffering and euthanasia of unwanted dogs.

With my own clients, I discuss the complexity and inconsistency of the evidence, the general trends that seem to be apparent, and the important of making individualized decisions based on all the relevant factors, including age, breed, sex, intended purpose, and the circumstances of the owner. For the most part, I recommend neutering of females before their first heat, though the evidence is still not ironclad and more work needs to be done to elucidate the details of potential risks and benefits in different breeds and with different neutering ages. For males, I no longer see a compelling reason to neuter unless there is clear evidence of aggression towards other dogs, however I emphasize to owners that they must be aware of the added responsibility to prevent roaming and unwanted breeding.

These recommendations are different from those I gave when I first graduated from veterinary school, and they have changed as a result of changing and improving evidence. Likely they will continue to evolve as more research is done and we have a better understanding of the issue.

Table 1

Table 2

Table 3

Posted in General | 37 Comments

Dr. Barbara Royal Reminds us that the AHVMF Opposes Science-Based Medicine

Posted on July 9, 2014 by skeptvet

I write regularly about the American Holistic Veterinary Medical Association (AHVMA) and its fundraising arm the American Holistic Veterinary Medicine Foundation (AHVMF). These organizations are very much the tip of the spear for pseudoscience in veterinary medicine. Unfortunately, despite peddling ideas which are often fundamentally incompatible with well-established science and with the evidence of history that science is the best way to understand the world and improve health, these organizations are remarkably effective at pretending to have a genuine interest in scientific research of alternative therapies, raising large sums of money (AHVMA and AHVMF financial statements), and then using that money and that superficial appearance of accepting the importance of science to infiltrate academic institutions and veterinary organizations.

From time to time, the leaders of these organizations share their true feelings about science and science-based medicine, and I feel it is useful to draw attention to those so that, hopefully, the truth beneath the façade will be visible and both veterinarians and pet owners can make fully informed judgments about the intentions and agendas of these groups.

In a recent interview in Natural News, a well-known platform for promoting the most egregious anti-science quackery, the president of the AHVMF, Dr. Barbara Royal, presented an honest and quite bizarre characterization of science-based veterinary medicine.

Dr. Barbara Royal, president elect of the American Holistic Veterinary Medical Foundation, believes that mainstream American physicians and veterinarians are only educated in one way.

“MDs and DVMs learn a lot about surgery, a lot about medications, a lot about disease…but they don’t learn about the causes of health.”

Royal believes in an integrative approach to health, NOT interventionist medicine. She strives to focus on supporting pet health as a first priority instead of treating disease after it has developed. This philosophy is challenging the status quo. Today’s mainstream veterinary students are taught to treat pets with an approach emphasizing drugs and surgery.

Throwing a drug at the problem often leaves pets with side effects and an impending death. The philosophy of, “take this drug, we don’t really know how it works, good luck,” is a symptom cover-up approach that reaps more consequences in the end. Although mainstream veterinarians mean well and want to help, their philosophy – the way they were taught – is a patch work that ultimately leads to unintended consequences.

The clichés that conventional medicine treats only symptoms without any interest in the underlying causes of disease, that preventative healthcare is ignored by conventional veterinarians, and that science-based medicine ignores all interventions except surgery and pharmaceuticals are often repeated by proponents of alternative approaches despite being obviously and manifestly untrue.

Dr. Royal offers a few tidbits from the alternative perspective the AHVMF advocates, which include further clichés, such as blaming mysterious toxins, conventional diets, vaccines, and of course medicines (ah, I mean “drugs”) for illness and suggesting that without the products of science-based medicine our pets would be living natural, healthier lives. It is hard to imagine anyone making such an implication with a straight face given the overwhelming evidence that human health and longevity has improved dramatically since the advent of the scientific approach to a degree unimaginable during the thousands of years of pre-scientific approaches to health that sound very much like the “natural” approach the AHVMF advocates, complete with ancient healthcare strategies based on pseudoscience and mysticism like Traditional Chinese Medicine, Herbal Medicine, Acupuncture, and so on. (See the graphs below for a couple of illustrations of this well-documented history)**

She encourages pet owners to eliminate corn and wheat from their pet’s diets, because these are pro-inflammatory, unfamiliar ingredients to an animal’s body. She teaches about pet food processing methods that create heterocyclic amines and acrylamides, which are potent carcinogens.

She talks about concepts like the lack of moisture content in kibbles which lead to dehydration in the animal. She talks about the amount of glycotoxins in dog food that cause inflammation in pets.

Royal also warns against overdoing those things that could cause harm. She teaches not to over medicate or over-vaccinate a pet, teaching how this interferes with an animal’s natural ability to heal.

Like other leaders of these organizations, Dr. Royal pays lip service to the value of science when speaking to those who truly do recognize the importance of the scientific approach, but when speaking with fellow believers in alternative therapies, she makes no reference to scientific evidence at all but is quick to  offer the well-respected testimonial/anecdote as validation for the preceding rejection of science-based medicine and its philosophy and methods:

On the inspiring stories page of the AHVMF page, one can find many testimonials of pets cured through holistic means.

Despite being psychologically compelling, such miracle stories are not a reliable way to evaluate whether a healthcare intervention is safe and effective. But they are very effective as a marketing tool, which ultimately matters more to the AHVMA and AHVMF that inconveniences such as what is true.

The fact that Dr. Royal and others in these organizations have a deep, genuine faith in their methods is not in itself objectionable. What is disturbing, and dangerous for our patients, is that they seem able to obscure the fundamental rejection of science and science-based medicine at the core of their ideology.  The fact that an organization run by individuals who blithely mischaracterize conventional medicine, as Dr. Royal does in this article, and who reject the basic philosophy or the need for science can be welcomed as an affiliate within the American Veterinary Medical Association and as a source of funding for research and educational activities at schools of veterinary medicine is bizarre and disturbing. The growing influence of these organizations does not bode well for the future of veterinary medicine as a profession or, more importantly, for the continued progress in healthcare that benefits our patients.
**EPSON MFP imageHere is a chart which reminds us that before the 20th century, and the advances in agriculture, sanitation, and medicine brought about by the accumulating scientific knowledge of the preceding two centuries, human life was short and few children could count on living to adulthood, much less a ripe old age. This pattern had remained unchanged for thousands of years despite the “ancient wisdom” of trial-and-error folk medicine now advocated by the AHVMA and AHVMF. The chart below, while more speculative that the one above, illustrates this based on all the evidence currently available.

life expectancy graph

 

This is the reality the AHVMA is so eager to ignore in favor of a naïve image of a Golden Age of health and well-being prior to the development of science and technology. No one can deny that the fruits of science have not always been benign or wisely used. But denying that overall human life is longer and healthier thanks to science than it ever was during the millennia we relied on more “natural” methods is irrational and dangerous.

 

Posted in General | 9 Comments

Happy 5th Blogiversary to Me!

Posted on June 24, 2014 by skeptvet

5th blogiversary

Though I’m a little late, I’m a forgiving sort, so I won’t be mad at myself for forgetting my blogiversary. June 4 marked five years of the SkeptVet Blog! The project has grown in so many ways. In the early days, I was excited to get fifty hits in a day, and in the last year it has been routine to get 800-1000 per day. Still small potatoes by Internet standards, but gratifying nonetheless. My goal has always been to provide a useful informational resource to pet owners and veterinarians, and to provide an alternative perspective on many therapies for which the only information on the internet is biased and unjustified marketing hype. The more people who know the blog is here, the more useful it is likely to be.

I have also expanded to discuss a much wider range of topics, even leaving the domain of alternative medicine more and more often. And in writing articles every week for five years, hopefully I have become a more effective communicator. I cringe when I look at the style and tone of some of my early posts, but I choose to view that as a good sign since it must mean I have grown and changed.

Writing this blog has provided me with opportunities to talk about evidence-based medicine more widely, to veterinarians and students and the general public, through my own lectures and presentations, writing opportunities, and interviews in the media. Hopefully, these activities will add an under-represented perspective, that of science and skepticism, to conversations within these communities about the best way to protect and restore health in our animal companions. I’ve never claimed to have all the answers, but I think I have some important and useful questions.

And writing this blog has certainly stimulated discussion and feedback. I have reviewed the negative comments before because I believe they are instructive in understanding the beliefs, values, and emotions that support pseudoscience and impede the effective use of science to improve veterinary medicine and animal health. But as an anniversary present to myself and those who find this project useful, I thought I’d review some of the positive feedback I’ve received. As well as being fun, this will help maintain the energy needed to keep going, which I fully intend to do. (All comments have been anonymized).

As a side note, another way to maintain this energy is going on vacation, which I will be doing starting this weekend. So activity, including responses to comments and emails, will be pretty light here for a few weeks. Never fear, I will keep up as best I can while I’m travelling, and I will dive back in with responses to your questions and comments and new articles with renewed vigor when I get back.

Finally, I offer a heartfelt “Thank you!” to all who have taken the time to provide supportive comments, questions or suggestions for topics to discuss, and thoughtful, substantive criticism. Your feedback does a great deal to neutralize the vacuous and angry responses a blog such as this inevitably draws and to maintain my faith in the possibility of civil, rational, fact-based discourse.

Thank you very much for taking the time to respond to my email and for providing a thoughtful response. .. Thank you for all the information you provide on your website as well.

Thank you. I asked my vet about XX again after I read your post…. I want to thank you for your honest “second” opinion before I started her on both meds. Knowing the possibility of “unknown” side effects makes me want to rethink…

Thank you very much for the information. .. Again, your advice is much appreciated in a difficult time for us.

I was very pleased the day I found your blog. You have excellent epidemiologic insight, which is rare among vets…. So, I applaud you for your post on media coverage of healthcare research.

Thank you so much for your timely response and thoughtful answers. I greatly appreciate you effort.

Thank you so much for your reply and the referenced article…Thank you so much for taking the time to answer my original email. I never expected to receive a reply, let alone a quick reply. The ACVIM Consensus Statement was extremely helpful.

I am so touched that you have replied so promptly and it is really fantastic to have such a well considered and scientifically based answer. Thank you very much, I truly appreciate it.

Thank you so much for your quick and detailed reply! I will be reviewing the links today. I so appreciate the work that you do and your personal reply to inquiries. I know that you receive a lot of negative feedback but I know there are also many, including myself, that appreciate your time, research, analysis and pragmatic consideration.   As a pet owner who loves her dog, I of course am in search of anything that won’t harm but could be helpful beyond the standard of care that we will be doing. I try to do diligent research on any recommended unconventional treatments.  Not just for my own dogs but when I am assisting in the treatment of patients at our hospital…This is something I take very seriously.  Reviewing your information I hope will help me make the best, most informed decision…

I just wanted to thank you for your blog. I have training in research design and statistical methods, but not as a biologist or veterinarian. I always want to read peer-reviewed research when something is wrong with my dog, but don’t understand the medical terms. Your blog is really a godsend. Keep up the good work!

I had originally intended to reply…in a private e-mail with encouragement and praise for speaking up for the rest of us in the “silent majority.”  Its a tough role to play and I continue to be impressed with your eloquence…Keep it up.

I’m so glad to see some common sense in the world. Your blog exposes a lot of the craziness which I really appreciate, especially coming from an MD background… It’s fascinating to me how quickly people gravitate towards alternative medicine, towards theories that sound magical and assume that they are just correct without any scientific evidence to back it up. Thanks for keeping it real!

I did try do my own review from primary literature, but I do not know the journals or the field at all, so your review was exactly what I was looking for, thank for that! My local vet now has a few extra facts to consider…As for the rest of your site, I enjoyed that too, and I’m very thankful that you take strong, and informed standpoints on CAM issues.

Good luck, and keep up the good work!

I wanted to drop a quick note to thank you for taking the time to post your thoughts and observations regarding various common and/or popular veterinary treatments…The net is long on anecdotes, short on science. Finding your blog has gone a long way towards filling the gap.

Just a quick thank you for your website and blog site. I’ve followed your sites for a while, and your citations to sources and reference materials are helpful in allowing me to share your information to family, friends, and our vets. The (sometimes) desperate urge to “do something” for our ailing pets clouds the minds of owners and vets alike, it seems. And some have a very hard time getting out the cloud.

First I wanted to thank you for posting your lecture, I shared it far and wide and hope that some of my colleges and friends were able to get what I was able to get out of it…Thank you for your response, your response far exceeded my expectations and I appreciate that.

You are doing a great service to pet companions of all stripes! we just struggled with putting down our beloved dogs in the past year, and the pressure to do all sorts of extraordinary but probably not effective treatments for them made it much more stressful.

Thank you so much for taking the time to reply!  Your message has helped very, very much.  We (pet people and their pets) are fortunate to have someone as thoughtful and generous as you are.

I’m new to your website as of today, came across it while searching for evidence-based information on dog food. What a great find! I completely appreciate your world view…Thank you for providing such a great source of well-researched and thought out information.

Just a quick note to tell you of my appreciation for you site. For years I have tried to educate my clients about the problematic proof supporting many of the alternative therapies other clinicians have been promoting… keep up the good work…

I appreciate your articles and perspectives. It’s so difficult to know how to best care for one’s pets in the face of so much contradictory information out there. .. Thanks so much!

Want to thank you for all of your efforts. Greatly appreciated and just hope that the folks who should be reading your site, somehow find it.

Thank you so much for your response. It is quite disheartening that there are so few veterinarians who are willing to speak out against organisations such as the American Council of Animal Naturopathy.

Skeptvet has superpowers It takes not only a extensive knowledge of vet medicine but the ability and time to put in writing that knowledge so others can understand the issues. I have seen other vets with extensive general small animal and human medicine knowledge. I have seen other vets that were great writers. But never a vet that had both knowledge with his ability to write. I find it difficult to believe only one person is at work here in this blog. It’s amazing what one person in the field of vet medicine is capable of accomplishing if they have the knowledge, training and dedication to do it.

Thanks for keeping it real, skeptvet, it’s frustrating to read some of the rants that occur here by those with an obvious ax to grind.

Skepvet, I’ve enjoyed the dialogue between yourself and dfg. I also appreciate your blog as source of information.

Thanks for the science-based common sense!

Thank you, Thank you !!! For writing such a clear, well documented and intelligent and thorough response and work.

Thanks for taking the time to compose this article…Your review was applicable and timely.

Hiya, just wanted to say and thanks. I’m getting a kitten and was considering a barf diet, but after doing my research, and coming across your site, I’m relieved to say I won’t be feeding my pedigree any raw food.

I just found this blog, and I’m so glad I did. There is way too much woo and pseudo-science out there for people who genuinely care about companion animals to wade through when trying to make informed choices on anything from medication and nutrition to training techniques.

Caveat emptor. Skeptvet, thank you for taking the time to elaborate. I found it helpful and I hope that others will as well.

Thank you for providing this valuable perspective.

I am still looking for the product I need. But, in the meanwhile I read your blog, loved it. Made perfect sense to me. And such a perfect way to confuse the writers, with fact.

Thanks for what you do generally, and specifically for providing a clear and reasonable overview of the literature on this issue. Like you and many others, I find the lack of quality controlled research here unfortunate

I am SO happy to have found your website! Will be following faithfully form now on. Thanks!!

Excellent blog post, as always, Skeptvet. Thank you for all you do.

Thank you again for producing this blog. I’m sharing this entry as part of my ethical duty to spread knowledge about the inefficacy of homeopathy.

Thanks for yet another well presented summary of the fallacies of magical thinking,

Thank you so much for this excellent summary based on SCIENCE.

Someone needs to stand up to faith masquerading as science, and people who would try to twist evidence to support their own agenda. Someone needs to hold the high ground when such people start flinging ad hominem abuse and sarcastic crap in defence of their idealism. But it’s so hard, and most of the time it’s a thankless task. I feel for you.

Thank you so much for offering a balanced view point of this.

Thanks for the facts. I trust a well argued appeal to reason and peer-reviewed evidence over the numerous emotional online sources decrying the substance.

Thank you thank you thank you ! The Dr. Dean Edell of veterinary medicine

Posted in General | 6 Comments

One More Time: Dogs are not Wolves!

Posted on June 24, 2014 by skeptvet

Most everyone knows that dogs are descended from wolves. Anyone who has ever seen a dog and a wolf also knows that more than 10,000 years of active and passive selection by humans has had a dramatic transformative impact on the anatomy and physiology of the dog. Ancestry is not destiny, and the fact that dogs have wolf ancestors does not mean we should think of our pets as wolves or treat them as such.

I have made the point here many times that dogs are not wolves and that the notion of feeding them as if they were wild carnivores is lacking both sound logic and real evidence. A new study adds a small piece of additional evidence to the discussion.

Comparison of the fecal microbiota of wild wolves, dogs fed commercial dry diets and dogs fed raw meat diets. A. Sturgeon, C.M. Jardine, J.S. Weese. University of Guelph, Guelph, ON, Canada.

In this study, the authors looked at the microbial flora of 15 dogs (10 fed commercial kibble and 5 fed a raw meat-based diet) and 10 wild wolves and classified the types and proportions of bacteria present. The flora of the GI tract is a reflection of both the diet and the inherent biology of a species. The findings, not surprisingly, were that the flora of wolves and dogs were quite different. Wolves had a more variable flora than dogs, likely due to a more inconsistent diet. It is worth noting also that feeding dogs a raw meat-based diet did not alter the microbial flora to make it more like that of wolves.

As I have said many times, I don’t believe we have sufficient evidence to make strong claims about what is the optimal diet for dogs overall, much less for individual dogs with their own unique circumstances and needs. Conventional commercial diets are clearly sufficient to avoid obvious nutritional deficiencies, and millions of dogs live health, happy lives eating them. However, it would not surprise me at all to find that changes in these diets, or even a switch to a markedly different way of feeding our canine companions, would improve health and longevity in our pets. Science is a process which is never finished and in which all knowledge is provisional and subject to re-assessment.

However, we do our pets no favor by making dramatic changes in established feeding practices based on unsubstantiated theories or hunches without adequate evidence. As far as raw diets are concerned the theory behind them is weak, and there is currently little evidence concerning their health effects. More work will need to be done before it makes sense to claim these diets have benefits which outweigh their risks. The argument that we should be feeding these diets to our dogs because they are fundamentally wolves inside is not supported by the existing evidence, and it is not a sound reason to experiment with our pets’ health.

Posted in Nutrition | 49 Comments

Hilarious Takedown of Dr. Oz & Big Supplement’s Lobbying Against Public Health Regulation

Posted on June 23, 2014 by skeptvet

John Oliver of Last Week Tonight (formerly of The Daily Show) provides a thoughtful, informative, and very funny report on the recent grilling of Dr. Mehmet Oz by Senator Claire McCaskill ansd the shameful success of the supplement industry lobbying Congress (especially Senators Orrin Hatch and Tom Harkin) to prevent sensible publich health regulations for dietary supplements. Bravo John!

 

Posted in Humor | 2 Comments

BSAVA Statement on Complementary & Alternative Medicine

Posted on June 20, 2014 by skeptvet

Organizations representing veterinarians are fundamentally political in nature, and their leaders respond to the will of their constituencies. I have often written about the American Veterinary Medical Association (AVMA) in the context of alternative therapies and evidence-based medicine. While the organization has adopted some policies I believe are scientifically sound and in the best interests of veterinary patients and clients as well as veterinarians, there is no question that the group answers to veterinarians first and foremost, even when these conflict with the scientific facts or the interests of clients and patients. And within the veterinary profession, there are different and often competing constituencies that leaders of groups like the AVMA must respond to.

In regards to complementary and alternative veterinary medicine, CAVM, I have often been disappointed in the AVMA’s positions, though I understand the political realities that shape them. There is a constituency of pro-CAVM veterinarians which is small but vocal and well-funded. The constituency devoted to science and evidence-based medicine is smaller, less vocal, and not nearly as well-funded. And the large majority of veterinarians appear to have little interest or opinion concerning CAVM. This leads the AVMA as a whole to rather tepid positions on CAVM that reflect the political landscape far more than the scientific evidence.

The handling of the resolution introduced into the AVMA House of Delegates in 2012 discouraging the use of ineffective therapies, and specifically identifying homeopathy as such a therapy, illustrates the politics of CAVM within the AVMA. The science conclusively shows homeopathy to be nothing more than a placebo, despite attempts by homeopaths to claim otherwise, and the AVMA’s Council on Research supported this conclusion. However, the House of Delegates voted overwhelmingly against the resolution anyway because of vociferous opposition from pro-CAVM veterinarians, a general lack of interest in the scientific issues on the part of most members, and a deep cultural reluctance among veterinarians to criticize the practices of colleagues.

The AVMA also has a general statement on CAVM which used to be a fairly thoughtful, though still politically circumspect, document. It at least identified some core issues raised by the use of CAVM:

The theoretical bases and techniques of CAVM may diverge from veterinary medicine routinely taught in North American veterinary medical schools or may differ from current scientific knowledge, or both.

The AVMA believes that all veterinary medicine, including CAVM, should be held to the same standards. Claims for safety and effectiveness ultimately should be proven by the scientific method….Practices and philosophies that are ineffective or unsafe should be discarded.

The AVMA does not officially recognize diplomate-status or certificates other than those awarded by veterinary specialty organizations that are members of the AVMA American Board of Veterinary Specialties (ABVS), nor has it evaluated the training or education programs of other entities that provide such certificates. Recognition of a veterinary specialty organization by the AVMA requires demonstration of a substantial body of scientific knowledge. The AVMA encourages CAVM organizations to demonstrate such a body of knowledge.

The quality of studies and reports pertaining to CAVM varies; therefore, it is incumbent on a veterinarian to critically evaluate the literature and other sources of information. Veterinarians and organizations providing or promoting CAVM are encouraged to join with the AVMA in advocating sound research necessary to establish proof of safety and efficacy.

In this document, the AVMA refrained from passing judgment on the scientific merits of CAVM, but it at least acknowledged that science was the standard by which veterinary therapies should be judged and that, as of yet, few CAVM practices have met such a standard.

The new AVMA position on CAVM has been stripped of essentially all content and says merely that all therapies should be held to the same standard (without indicating what that standard should be) and that nobody should break the law. This revised statement moves further away from the notion that veterinary medicine is, or should be, a science-based profession. It reflects the growing political reluctance to make critical, evidence-based judgments about claims or practices so long as a licensed veterinarian is employing them.

Other veterinary organizations have been more faithful to the role of science as the foundation of veterinary medicine, with many specifically acknowledging the unacceptability of homeopathy in a science-based profession, and many identifying science and evidence-based medicine as essential to veterinary medicine.

A recent statement on CAVM from the British Small Animal Veterinary Association (BSAVA) takes a fairly moderate, political position on the issue of CAVM, though still one more robust than that offered by the AVMA. Like the previous AVMA statement, the BSAVA document acknowledges science and scientific research as the essential foundation for veterinary medicine, and explicitly endorses and evidence-based approach:

The BSAVA recommends that owners consider the evidence for a particular treatment and the qualifications and experience of the practitioner before embarking on any complementary or alternative therapy for their pet.

The BSAVA strongly recommends that whenever possible treatment decisions are based on sound scientific evidence to support the safety and efficacy of the therapy.

Assessing the evidence

Some people, including owners, therapists and veterinary surgeons, may perceive that the therapies work as a result of belief in the therapy (placebo effect); anecdotal evidence (extrapolation from hearsay or personal experience of a single or small number of cases) or errors in inference (cognitive bias).

There are three factors strongly associated with whether or not any one medical treatment is likely to be efficacious:

1. A rational scientific basis

Modern medicine works, and it works because it is founded on a scientific base. Although not all treatments used in conventional medicine have a strong evidence base in the sense of rigorous clinical trials showing their efficacy they do have a rational scientific / pathophysiological basis for their use.

2. Degree of certainty

The effects of some treatments are so clear cut that further testing is not required. It has famously been pointed out that rigorous clinical trials are not needed to prove that parachutes reduce morbidity and mortality among people falling from aeroplanes. Similarly, one does not need rigorous trials to show that intravenous anaesthetics cause a rapid, profound loss of consciousness suitable for carrying out surgery. However, the effects of many treatments are much less certain; e.g., they are less closely associated in time with their effect, or the effect caused is much less dramatic, smaller and/or more variable in magnitude and/or time of onset. In such circumstances, given the variable time courses of many diseases, it can be remarkably difficult to determine whether a given treatment is actually efficacious or not.

3. Evidence

When there is anything less than absolute certainty about the efficacy of a treatment, then evidence is important in deciding whether a treatment is safe and efficacious. However, history has also shown that evidence – both in the form of clinical experience and individual clinical research results – can be misleading. The process of evidence-based (veterinary) medicine exists to improve our confidence by formally and systematically searching for all of the relevant evidence and formally and systematically grading the quality and reliability of that evidence.

The organization also acknowledges that the evidence for most CAVM is poor and that safety or efficacy is largely unknown for many CAVM practices:

Health claims for many complementary and alternative therapies are far in excess of the available scientific data, and sometimes in frank contradiction to scientific evidence.

In making decisions about the use of complementary and alternative therapies it is important to consider their safety and efficacy. Many people assume that all complementary and alternative therapies are natural and therefore safe, but this is not always the case. All therapies may produce unwanted side effects or may interact with other therapies. In the case of alternative therapies it is also important to consider the welfare implications of withholding conventional treatments.

There is a great deal of variation in both the degree to which various complementary and alternative therapies have been scientifically tested, and to which such testing has provided evidence supporting their efficacy.

While I believe it would have been appropriate to go further and acknowledge that at least some CAVM practices are completely without merit and should be discouraged, such as homeopathy and so-called “energy” therapies, I think this is a solid statement supporting the important role of science in veterinary medicine. Relying on science to understand and predict nature has led to far greater health and well-being and far less physical suffering than human beings, and our animal companions, experienced in all the thousands of years before we developed the scientific method. Acknowledging the unparalleled power of science to guide us to the right answers in healthcare is essential in maintaining and extending the gains science has allowed medicine to achieve.

This statement seems to indicate that the constituency of the BSAVA, like that of other veterinary groups in Europe and Australia, is moving in the right direction with respect to deepening the reliance on science and evidence-based medicine in the veterinary field. Sadly, the recent actions of the AVMA would suggest that here in America, as seems evident in many other areas, we are moving in the wrong direction, away from rationalism and science and towards an epistemology that privileges personal experience and belief over objective, scientific evidence. This is not in the best interests of our patients, our clients, or our profession.

Posted in Law, Regulation, and Politics | 1 Comment

JustFoodForDogs Brings Us Some Classic Marketing Masquerading as Science

Posted on June 12, 2014 by skeptvet

I have written about the issue of homemade pet diets here several times (1, 2, 3, 4). They are appealing to some owners because they appear more “natural” than commercial dry or canned diets, which is supposed to imply they are better for pets. And, of course, many proponents of alternative medicine make hysterical and unsupported accusations about the dangers of conventional pet diets.

People also equate conventional commercial pet food with what is typically called “processed food,” though they are entirely different things. Human snack foods and other processed foods are laden with excessive sugar, salt and fat and generally nutritionally poor. Commercial pet foods, if properly formulated and manufactured, are nutritionally balanced to a greater degree than our haphazard diet of whatever looks appealing in the moment, even when we the packaged junk foods are avoided.

Homemade diets can be perfectly healthy, and there are circumstances in which a diet formulated for the specific needs of a particular pet is better than any commercially available diet. And fresh food is certainly attractive to many pets. But the dramatic claims of health benefits made for them are entirely unproven, and the existing research suggests most recipes for homemade diets, even those promoted by veterinarians, are not appropriately balanced nutritionally and not ideal for long-term health. I encourage anyone interested in preparing food at home for their pets to consult with a board-certified veterinary nutritionist for guidance.

I recently ran across a press release from a company which appears to be trying to cash in on fears of commercial pet food and the appeal of homemade diets in order to sell—you guessed it, their commercial pet food. Reminiscent of the “just like homemade” marketing approach often used to sell packaged foods for people,  JustFoodForDogs makes heavy use of terms like “scientific” and “evidence” in their marketing to suggest that dry commercial diets and the ingredients they contain are unsafe and that their packaged frozen cooked diets are better. While these diets appear to meet all the same standards for balanced nutrition of other commercial diets, including AAFCO feeding trial tests, the evidence offered for their superiority is so far scant.

One unpublished study funded by the company and run by one of their veterinarians is referred to in their press release as “groundbreaking” and “game changing.” Science by press release is always a bad sign (anybody remember “cold fusion?”), but the presentation of the study is clearly designed to maximize its marketing value without providing any of the information that would be needed to determine if the methods were really appropriate.

Twenty-one dogs of unspecified breeds were fed some of the company’s diets (the details are not reported) and basic bloodwork and exams were conducted at the beginning of feeding the diet and again at 6 months and twelve months. No control group, no blinding, no pre-specified outcomes or hypotheses, no reported accounting for repeated measures or multiple comparisons in the statistical analysis, no discussion of any other aspects of the dogs health or environment, and overall none of the hallmarks of an actual controlled clinical study. All of this would be fine of the purpose were merely to explore the effects of the diet and generate hypotheses. But the company clearly intends to present these results as earthshattering, paradigm-shifting research that (coincidentally?) favors their product.

And after setting up everything with no apparent effort to control for the obvious risk of bias, what were the reported results? One kind of blood protein, globulins, went up (by how much isn’t disclosed). Some kinds of white blood cell numbers increased (again, by how much isn’t disclosed, but the numbers were apparently still within the range of normal). And one measure of red blood cells increased, though another did not.

Given the comparisons of many different values with no explicit reason and no reported use of statistical methods to control for making them, it is almost guaranteed some values would change to a degree judged “statistically significant.” This is not the same thing as medically significant, and there is no evidence these changes had any clinical relevance, especially with no control group for comparison. But the company promotes the results as showing their foods “could benefit immune health” and that if the purported trends in the blood values continue for the animals’ lifetimes “we may see a decrease in chronic diseases such as cancer, renal failure, kidney disease, inflammatory bowel disease, dental disease, etc.”These results certainly don’t support anything even approaching such claims.

The hypothesis that fresh foods could have health advantages over extruded kibble or commercial diets is not an unreasonable one, and I am open to the possibility this might be true. But this is not something we can simply assume without evidence, and that evidence does not yet exist. Furthermore, the claims made about the dangers of conventional commercial diets are rarely supported by evidence either, whereas there is abundant scientific research and real-world experience showing that pets can live long, health lives on these foods.

If the folks behind this company genuinely believe their claims about health and nutrition, and I have no reason to think they don’t, then they should make an effort to design and conduct properly controlled scientific research to evaluate their hypotheses. But they do a disservice to pets and pet owners when they perform “studies” clearly designed with marketing rather than science in mind, hype the results to an extreme degree, and then use this as a marketing strategy to promote their own products.

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