New Review Finds Little Evidence that Nutraceuticals Help Animals with Arthritis

I have written extensively about various supplements and herbal treatments for arthritis. For the most part the evidence seems weak for all of these products, though there are a couple of suggestive studies that might lead to demonstrably effective treatments someday. I have also talked about the need for application of rigorous, explicit evidence-based medicine techniques (EBM) in veterinary medicine. A recent paper in the Journal of Veterinary Internal Medicine does an excellent job of illustrating EBM methods, and its subject is the use of nutraceutical for treatment of osteoarthritis in animals.

J.-M. Vandeweerd, C. Coisnon, P. Clegg, C. Cambier, A. Pierson, F. Hontoir, C. Saegerman, P. Gustin, S. Buczinski. Systematic Review of Efficacy of Nutraceuticals to Alleviate Clinical Signs of Osteoarthritis. Journal of Veterinary Internal Medicine. 2012. Epub ahead of Print.

The authors adapted the CONSORT statement and recommendations from the Centre for Evidence-Based Medicine at Oxford to design an explicit and detailed scoring sheet for research trials involving nutraceuticals for osteoarthritis. This sort of transparency, and establishing criteria for grading evidence in advance, are important aspects to an evidence-based review, which help to minimize the potential impact of personal bias on the results.

The authors then conducted a thorough literature search for articles in English and French that concerned the use of common nutraceuticals in arthritis treatment. A total of 67 articles were found, of which 22 met the inclusion criteria of the review (controlled clinical trials evaluating clinical signs of pain or locomotion). The literature search terms are presented in the report in a way that makes replicating the search straightforward.

An exhaustive evaluation of these 22 studies was then conducted, with a grading of the quality of evidence for the following nutraceuticals:

Glucosamine
Chondroitin Sulfate (various forms)
Undenatured Type II Collagen
Avocado and Soybean
Gelatine Hydrolysate
Omega-3 Fatty Acids (aka fish oil)
Hydroxycitric Acid
Green-Lipped Mussel Powder
Special Milk Protein Concentrate
Indian and Javanese Turmeric
Various combinations of these ingredients and such as manganese, vitamins, amino acids, chromium, and more

The conclusions were quite straightforward:

The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs…The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs.

The authors also touched on many of the limitations of the available literature, not only the small numbers of studies and subjects, but the lack of replication, the tendency for all the research on a single subject to come from one researcher or research group, the lack of motivation for studies given the lack of effective regulation of dietary supplements and many others.

This is an excellent example of the application of EBM methods to veterinary questions. While the available evidence is often limited in quantity and quality, we need to critically appraise what there is in order to make the best clinical decisions. I think the methodology used in this paper is a model for how such reviews can be conducted and how they can be useful to general practitioners.

My only quibble was with the conclusion the authors reached concerning fish oils. I have previously reviewed three of the four studies they evaluated (here and here), and while I agree that they are generally good quality studies, I think the results are less convincing than the authors claim or than this review suggests. It can be difficult to balance an objective, checklist-based evaluation of the evidence, which reduces the influence of reviewer bias, with the need for a judicious assessment of the details of the evidence, and I think the authors of this review generally do a good job. But I think they reach the wrong conclusion with regard to the fish oil question.

Below is a detailed evaluation of the findings of each study, which I think illustrates why the few positive data reported provide only weak evidence of a benefit for fish oils in treatment of arthritis.  

A.    Dose-titration effects of fish oil in osteoarthritis dogs.  

1.     Semi-objective measure (veterinarian clinical assessment)

Of five measures assessed at four time points, all measures improved for all groups. Without a no-treatment arm, it is impossible to know how much of this apparent improvement is an artifact of study participation.

Only two measures improved significantly more for highest dose diet compared with the lowest dose diet (with no differences between the medium and lowest dose diets). These improvements were small and of dubious clinical significance: from 1.68 to 1.40 (~17% improvement) and from 2.00 to 1.64 (~18% improvement) on a scale where 1-no signs, 2-mild signs, 3-moderate signs, 4-severe signs). 

2.     Subjective measure (veterinarian estimate of overall change based on exam and owner input)

Veterinarians were asked, based on their own assessment and owner input, how much over the 90 days of the study they thought the diets had slowed or accelerated the dogs’ arthritis, or if they had no effect. All diets were believed to have slowed the progression of the disease, with the highest dose diet scoring 2.32 and the lowest dose diet 1.99 on a scale of 1-significantly slowed, 2-slightly slowed, 3-no effect.

Veterinarians were then asked, based on their own assessment and owner input, how much over the 90 days of the study they thought the dogs’ arthritis had changed. All dogs were believed to have improved, with those on the highest dose diet scoring 2.55 and those on the lowest dose diet scoring 3.15 on a scale of 1-extreme improvement, 2-moderate improvement, 3-slight improvement, 4-no effect. 

  1. A multicenter study of the effects of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.

Reduction of the carprofen dose was the stated goal of the study, and the dose decreased for both groups. The control diet group dose decreased over 12 weeks by an average of 0.59mg/kg/day (from 4.14 to 3.58mg/kg/day, ~14%). The test diet group dose decreased by an average 1.13mg/kg/day (from 4.39m to 3.26 mg/kg/day, ~26%). The final dose differed between the two groups by 0.32mg/kg/day.

C.    Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs 

1.     Semi-objective measure (veterinarian clinical evaluation)

Out of five clinical measures over three time periods, there were no significant differences between control and test diet groups.

2.     Subjective measure (owner survey)

Out of thirteen measures over three time periods, there were two measures that differed significantly between groups at the first evaluation and one other measure that differed significantly at the second and third time period. No express statistical controls for making multiple comparisons were described despite p-values being reported for fifty-four different comparisons.  

D.    Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. 

1.     Objective Measure (force plate analysis)

Two measurements for each group were compared at two points in time and then a comparison was made of the percentage change in these measurements for both groups over the intervening period. Of the total of eight comparisons, one was significantly different between groups. 

2.     Semi-objective measure (veterinarian clinical evaluation)

Of five measures compared between groups at two points in time and in terms of change over time, the test group improved more than the control group in terms of two measures. This was the same measure of effect as used in Study 10, in which no such difference was seen. 

3.     Subjective measure (owner survey)

Of thirteen measures evaluated at two points in time, there were no significant differences between groups. This was the same measure of effect used in Study 10, in which three of the measures did differ at some of the time points.

References
1.     Fritsch D, Allen TA, Dodd CE, et al. Dose-titration effects of fish oil in osteoarthritis dogs. J Vet Intern Med 2010;24:1020–1026.

 2.     Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effects of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:535–539.

3.     Roush JK, Dodd CE, Fritsch DA, et al. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc 2010;236:59–66. 

4.     Roush JK, Cross AR, Renberg WC, et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:67–73.

 

Posted in Herbs and Supplements, Science-Based Veterinary Medicine | 6 Comments

Crananidin: Cranberry Extract for Urinary Tract Infections in Dogs and Cats?

The question of whether cranberries, in some form, have value in treating or preventing urinary tract infections (UTIs) is a pretty old one. Mark Crislip at Science-Based Medicine has written a nice summary of the topic, and he has found over 100 references dating back to 1962. Like most herbal remedies, it has traditionally been thought helpful for a wide variety of unrelated disorders, but it is now pretty firmly established in most people’s minds as useful for UTIs.

Unfortunately, as usual the subject is more complicated than is generally realized. The theoretical justification for using cranberry to treat UTIs used to be that it acidified urine and made it less hospitable for bacteria, however that is no longer believed to be true. The current theory is that chemicals called proanthocyanidins interfere with the attachment of bacteria to the bladder wall, making it easier for the body to eliminate these bacteria and harder for infections to get started.

This is certainly a plausible mechanism established  by in vitro studies. The trouble is that the proanthocyanidins inhibit attachment only for E.coli with little hairs called fimbriae on them. There are many other bacteria that can cause UTIs, and there isn’t yet any evidence that proanthocyanidins affect these. And in humans fewer than 20% of E.coli in bladder infections have fimbriae, so theoretically, these chemicals should be only be useful in preventing recurrent infection in a small minority of cases. (Interestingly, the vast majority of E.coli from kidney infections are fimbriated, so cranberry could possibly be more useful in these cases). There is also the problem that no one has actually proven that oral cranberry leads to proanthocyanidins getting into the urine, or being biologically active when they get there.

As Dr. Crislip points out, though, the theoretical mechanisms are not so important if the remedy doesn’t actually work in clinical trials. So does it? Well, there is still no consensus, since some trials show and effect and others don’t. The best that can be said as of now is that cranberry probably isn’t useful for treating UTIS and it may or may not be useful for preventing them.

Despite this uncertainty, the popular belief that cranberry products are useful for urinary tract infections in humans makes it inevitable that such products will be marketed to pet owners for UTIs in dogs and cats. As in humans, many UTIs are caused by bacteria other than E.coli, and I am not aware of any research on the proportion of fimbriated E.coli in canine and feline UTIs, so the theoretical rationale for this remedy is even weaker than in humans. But a quick Google search shows plenty of veterinary versions on the market anyway, often with pretty confident claims.

I recently came across some marketing materials for one of these, Crananidin from Nutramax. They are careful to avoid any treatment or prevention claims, since that would violate the Dietary Supplement Health and Education Act (DSHEA). However, they try pretty hard to suggest a benefit and even superiority over their competitors despite the absence of any clinical trial evidence.

The Nutramax literature has a nifty little graph of bioactivity in the dog purporting to show that “by 7 days the average bioactivity is over 78% at inhibiting E.coli.” They cite two articles to support this statement. One is an NMR study of the molecular structure of proanthocyanidin, and the only bioactivity data is from mixing fimbriated E.coli with human red blood cells and some cell-surface-receptor coated plastic beads in vitro (interestingly, this study was funded by Ocean Spray). There is no testing or discussion of clinical effects, and no data concerning dog urine. There really seems no way to interpret this citation other than being deliberately misleading.

The other reference is “Data on file, Nutramax Laboratories,” so I presume it is an unpublished in-house experiment. Unpublished data from a company selling a product that “proves” the product works, and is better than the competition, ought to be viewed somewhat skeptically, needless to say.

The marketing literature also has a little chart showing their product “passing” a test of bioactivity and all the competing products failing it. The references for this are the same, and since the published article has nothing to do with this issue, apparently the only evidence for this claim is unpublished in-house data from Nutramax. I’m not aware of any published clinical trials investigating this or any other cranberry product for use in UTIs in dogs or cats.

There also isn’t any evidence concerning the safety of cranberry products in dogs and cats. In humans, one concern is that cranberry juice has a lot of salicylic acid, so people with aspirin allergies or on anti-coagulant medications aren’t supposed to take a lot of it. But those are pretty rare issues in veterinary medicine. And some studies have shown it increases oxalate in the urine by up to 43%, so I wouldn’t recommend it for patients with a history of oxalate urinary tract stones (even though, again, this data is for people, and there are no studies I can find in dogs or cats).

Bottom Line
There is weak theoretical justification for using cranberry products for UTIs, though none of the supporting preclinical evidence involves dogs or cats. There is conflicting clinical trial evidence in humans, and no clinical studies in dogs and cats. There are weak theoretical safety concerns. And, of course, there is abundant marketing making bold statements unsupported by the little evidence that exists. You pays your money and you takes your chances. Fortunately (for Nutramax, if not for our pets), anecdotes claiming a benefit are easy to find, so there should be little trouble selling the products even without convincing evidence of safety or efficacy.

 

 

Posted in Herbs and Supplements | 8 Comments

Protandim: An Update from Science-Based Medicine

Last year I wrote a review of a dubious herbal combination product called Protandim. At that time, my bottom line conclusion was:

Bottom Line
The underlying theory used to promote this product, that anti-inflammatory and anti-oxidant effects are always safe and beneficial, is highly doubtful. There is only weak in vitro and animal model research to indicate that the ingredients in Protandim, or the combination product, have potentially useful effects on cells or biochemical markers. There is absolutely no clinical trial evidence to indicate Protandim has any of the claimed benefits in humans or animals. While the absence of evidence is not proof the product is unsafe or ineffective, it is absolutely a reason to be skeptical of wild claims of miraculous benefits. At best, using this product is simply rolling the dice and hoping for the best. That seldom works out for gamblers in Vegas, and it is not an appropriate approach to healthcare except in the most dire of circumstances.

Dr. Harriett Hall at the Science-Based Medicine Blog has recently provided an update on this product and a recent clinical study investigating it. The study was bizarre and it is amazing any ethics committee would approve it. It is also not prominently featured on the Protanidim web site, no doubt because no effect was seen. Here are a couple of highlights from Dr. Hall’s summary:

To recap their chain of reasoning: alcoholics might develop lung disease, that lung disease might be correlated with abnormal epithelial permeability, protein levels measured by bronchoalveolar lavage (BAL) might be a valid measure of permeability, permeability might be affected by underlying oxidative stress, and Protandim might reduce oxidative stress by stimulating the body to produce its own antioxidants. Do they perhaps think that lots of “mights” add up to a “mighty” argument?

The second listed author, Joe McCord, has a vested interest: he is an officer of the LifeVantage company, the manufacturer of Protandim. They explain that Protandim is “a nutraceutical with a lengthy history of use in homeopathic, Ayurvedic, and traditional Chinese medicine.” An interesting statement, since Protandim was invented only a few years ago by a person with no medical background and it was patented in 2007. Doubly interesting since it belies the common myth that natural medicines are not profitable because they can’t be patented.

They assessed alveolar epithelial permeability by measuring the total protein in bronchoalveolar washings. Total protein levels did not change in either experimental group. They also found no change in oxidative stress indices, epithelial growth factor, fibroblast growth factor, interleukin-1?, interleukin-10, liver function tests, or other blood chemistry tests. The one finding that was statistically significant was a significant decrease in plasma thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation — but that was only in the placebo group!

In short, Protandim was significantly (p<0.01) worse than placebo. No wonder they’re not bragging about this study!

Big Pharma gets a lot of criticism, but aren’t Big Supplement and Big Multi-Level Marketing every bit as guilty of self-interest, distortions, and profit motives? At least Big Pharma can’t make its big bucks without first demonstrating effectiveness and safety to the FDA with clinical trials.

Does Protandim provide any real benefit to its customers? I don’t know, and they can’t hope to know unless they do proper clinical studies.

 

Posted in Herbs and Supplements | 51 Comments

Raw, Cooked, and Dry Cat Diets–A New Study Examined

The debate about raw diets for pets is an ongoing “hot button” topic in veterinary circles. There is also a less heated but still vigorous debate about cat nutrition in particular and what form and composition constitutes the optimal diet for our pet cats. I have previously written about raw diets extensively, and I still hold the opinion that there is little reason to believe they are superior to cooked diets, including commercial pet foods (1, 2, 3, 4, 5, 6, 7).

The theoretical arguments advanced for using these diets are weak and often simply a form of the appeal to nature fallacy. “Natural” is not synonymous with “optimal,” so even for cats, which are obligate carnivores and often still actively predatory, actual experimental evidence is needed to justify the claim that the natural diet of raw, live small prey, or other raw diets promoted as equivalent, is better than the alternatives.  This is even more true for dogs, who have been so deeply altered by breeding and association with humans from their wild ancestors that it is a stretch even to claim there is a “natural” diet that domestic dogs should be eating.

While the benefits of raw diets remain unproven, there are legitimate concerns about risks, including infectious disease, parasites, and potential dangerous from specific components of some diets, such as bones. These risks do not yet appear dramatic, but they need to be weighed against benefits which can be substantiated by real research, which does not yet exist.

One recent study has compared a commercial kibble with both cooked and raw alternatives in a few cats, and some raw diet advocates are suggesting this is evidence in favor of the benefits of raw diets. Having looked at the study, I think it is an interesting beginning in terms of comparing different feeding options, but I am not convinced it provides significant evidence to support most of the claims made for raw pet diets.

K.R. Kerr, B.M. Vester Boler, C.L. Morris, K.J. Liu, and K.S. Swanson. 2012. Apparent total tract energy and macronutrient digestibility and fecal fermentative end-product concentrations of domestic cats fed extruded, raw beef-based, and cooked beef-based diets. Journal of Animal Science: 90: 515-522.

The study was nicely designed, though this also meant labor intensive, which likely contributed to the small sample size. Nine cats were each fed three different diets in rotation; a beef-based raw diet, the same diet cooked in a microwave to the standards for food safety recommended by the USDA, and a high-protein commercial dry diet. The cats ate each diet for 21 days. The last 4 days of each period, all feces and urine was collected for analysis, and on the last day a blood sample was taken.

The nutritional composition of the three diets was complete and roughly equivalent, though the ingredients of the commercial kibble were significantly different from the ingredients of the other two diets.  And of course the moisture content of the dry diet was significantly less than that of the others.

The only difference among the diets in terms of the bloodwork was a higher creatinine (a measure of kidney function, hydration, and protein metabolism) and triglyceride (a fat) in cats eating the cooked and raw fresh diets than in those eating the commercial dry diet. Though these values differed between the diets, they were within the normal range for all cats. 

Interestingly, there were no differences in the urinalysis values between any of the diets, and all the cats had very high urine specific gravity measurements (>1.064). One of the arguments for feeding fresh or canned diets is that the increased fluid content should improve hydration and reduce urine specific gravity, which is hypothesized to be useful in preventing and managing kidney disease. However, despite having water available at all times, the urine specific gravity was extremely high in all of these cats, and there was no difference between the kibble and the fresh diets.

Any interpretation of these numbers is speculative given the small size of the study, but one would expect the fresh diets to lead to lower renal bloodwork values and lower urine specific gravity than the kibble, particularly if they are to have any protective benefits against kidney disease. This data seems to undermine this hypothesis.

The amount the cats were fed was adjusted regularly to maintain an ideal body condition, so no differences in the effect of diet on body condition could be evaluated. Cats on the dry diet did eat more, in terms of volume and calories, than cats on the other two diets (which were not different from each other). This agrees with the finding that the dry diet appeared to be less digestible than the other two diets (which again did not differ from each other). 

The various measures of digestibility showed the dry diet to be between 4.2% and 11.7% less digestible than the cooked and raw fresh diets. However, as the authors state, “All diets tested in this experiment were highly digestible,” so the real-world significance of this isn’t clear. Presumably, a cat would have to eat a greater quantity of a less digestible diet and would produce more stool, but it is unclear how great a difference this might be or whether it would have any health implications.

Stool quality is often a marketing point for raw diet advocates. In this study, stool quality was evaluated on a 5-point scale:

1 = hard, dry pellets
2 = dry, well-formed stools
3 = soft, moist, formed stool
4 = soft, unformed stool
5 = watery liquid that can be poured

Cats on the dry diet had a higher score (average =3.3) compared to the other diets (which did not differ significantly at averages of 2.8 and 2.9). The ideal score is 3.0, so all of the diets generated a normal fecal consistency. Oddly, the dry diet appeared to lead to moister stools than the higher moisture content diets, which is the opposite of what one might expect.

A number of fecal compounds were measured, but the only conclusion drawn from the differences seemed to be again that the dry diet was less digestible and so led to greater colonic bacterial metabolism than the other two diets. However, the measurements were consistent with normal values seen in healthy cats. The health implications of this are unclear.

So what conclusions did the authors draw from these data?

Although the raw and cooked beef-based diets were more digestible than [the dry diet], all diets were highly digestible in this experiment.

Few differences in serum metabolites were detected

Urine variables did not differ among diets.

All scores of fecal consistency were within a desirable range, but cats fed [the dry diet] had greater scores

Carbohydrate fermentation was similar for all diets.

Fecal putrefactive compounds…were increased in cats fed [the dry diet] but were similar to values reported in the literature for healthy cats.

Because cooking may minimize risk of microbial contamination, and the results from the cooked beef-based diet tested herein were not different than the raw diet, cooking may be an appropriate modification to this feeding strategy

And, finally, the authors argued that more research is needed, which is certainly the case.

Overall, this study is interesting but doesn’t seem to offer much support to the claims made for raw, or even fresh high-moisture diets. No difference of any kind was reported between the raw and the cooked diet, and the vast majority of the measurements made did not differ between these and the dry kibble. And even the high moisture diets led to a high urine specific gravity, which would suggest less than optimal fluid intake.

The dry was slightly less digestible than the fresh diets, but all were easily and thoroughly digested. But as the authors state, “Because the ingredient composition of [the dry diet] was different than that of [the other diets], we acknowledge that the influence of the dietary composition and extrusion cannot be separated.” So it is not even clear if the difference found has to do with the form of the diet or simply the particular ingredients used. Even less clear is whether these differences have any implications for health or disease.

I certainly support further research into different pet feeding methods. My personal guess is that raw will not prove to have any benefits sufficient to outweigh the risks, though I do think feeding moist diets may turn out to be better for cats than feeding dry diets. Homemade diets may have some advantages, but these are probably outweighed by the persistent problems with nutritional adequacy and quality control unless a nutritionist is involved in formulating and supervising them.

I look forward to studies which either confirm these guesses or prove me completely wrong. However, until there is adequate research, these are simply guesses, not facts. The biggest concern I have about raw diet advocates is that they tend to make grand health claims far beyond anything supported by evidence. I wouldn’t be surprised if this paper is held up as evidence for those claims, but a close reading of it does not support that interpretation.

Posted in Nutrition | 18 Comments

Nzymes.com: Same Snake Oil, Different Day

Knowing that I have an interest in investigating the evidence behind claims for veterinary healthcare products, clients and colleagues sometimes pass along materials concerning veterinary supplements, herbal remedies, and other similar products and ask my opinion. Since there are hundreds, if not thousands of products marketed to pet owners to preserve or restore their pets’ health, I can only look into a few. However, the more of these I investigate, the more clearly I see the patterns of disregard for science and manipulation of the consumer that they have in common.

The latest in this category is a collection of products from a company called Nzymes.com. The website and pamphlet for this company exhibits nearly all of the warning signs of quackery. The company systematically tries to frighten the consumer by suggesting that pets cannot be healthy without their product and that the food and healthcare they are currently getting is inadequate.

Give Your Pet a Fighting Chance

If you are feeding your pet one of today’s popular processed pet foods, then chances are, your pet’s body is depleted of the primary enzyme precursors nature provides abundantly in all living foods.

The fact that we continue to feed our pets such enzyme-less food over an entire lifetime may contribute to the growing list of animal health problems we witness today including; osteoarthritis, inflammation, joint pain, hip dysplasia, pano, OCD, HOD, shedding, hair loss, dry skin, itchy skin, digestive disorders, gastritis, pet food allergies, epilepsy, fatigue, hot spots, and many other stress related symptoms contributed to by a weakened immune system.

The whole “living enzyme” argument is complete nonsense, and there is no evidence for the suggestion that commercial diets are nutritionally deficient or responsible for this long, redundant list of random symptoms and disorders. Some of these problems may be related to nutrition, but that has nothing to do with the claim made here, which is baseless.

But the pseudoscientific nonsense doesn’t stop there. The web site also blames pet food, vaccines, and medications for a variety of ailments, again without paying any attention to the real, and complicated, risks and benefits of these interventions. Classic quack nonsense like claims about the Pottenger cat “study,” about boosting the immune system, about mysterious “toxins” as a cause of unrelated diseases,  and about Candida yeast infections as a common cause of many health problems are all over the company web site.

So, what are they selling with all this fear? Apparently, miraculous panaceas with uncounted benefits and absolutely no risks! Since they aren’t allowed to claim they can actually prevent or treat any disease without having evidence to support it (though they effectively do, despite the Quack Miranda Warning here and there), they promise to “support”

Healthy Joint function, Healthy Muscle Function, Healthy Skin and Coat, Healthy Nervous System, Healthy Immune System, Healthy Circulatory System, Healthy Endocrine System, Healthy Lymphatic System, Healthy Digestive System, Healthy Urinary Function, Healthy reproductive Function, Healthy respiratory System, Healthy organ Function, General Overall Wellbeing

I like how they throw in “Healthy Organ Function” and “General Overall Wellbeing” just to cover any possible body part they might not have thought of. So if you’re afraid the imaginary causes of illness they mention have caused your pets’ problem, or might cause something bad someday, you can take comfort from knowing they this product can treat or prevent absolutely everything (except when it can’t, in which case it’s because of the food, the water, the medications, or anything else except the lack of benefit of their product). 

What, exactly, are the miracle elixirs offered by Nzymes.com?

Ox-E drops
This consists of 5% sodium chlorite, a chemical related to bleach. Properly diluted, this chemical is a safe disinfectant, killing infectious organisms through oxidation. With a pH of 13, if not diluted the chemical can cause burns, especially to the eyes and mucous membranes. Accidental overdose can be fatal.

The company advertises this as helping in “the removal of potentially dangerous free radicals and toxins,” and claims that is boosts the immune system, supports digestion, and enhances “performance.”  Impressive claims for a potentially toxic disinfectant that is actually an oxidant rather than an anti-oxidant.

As the accompanying quack Miranda warning attests, and a simple literature search confirms, there is absolutely no evidence for any of these claims. Plenty of testimonials are offered, of course, which is always the evidence of choice for products that are based on pseudoscience and have never been tested in any reliable way.

Antioxidant Treats
The antioxidant hype is a common marketing ploy for supplements because it’s vague, and there is enough suggestive preclinical research to suggest the general idea is plausible. Unfortunately, there are few clinical trials which show significant real benefits from particular anti-oxidants in particular conditions, and the evidence is growing that some such agents, such as Vitamin E, can actually increase the risk of disease.

The specific ingredients include Vitamin A, Vitamin C, Vitamin E, and a proprietary freeze-dried sprouted soybean meal claimed to contain:

The amount of the vitamins in the supplement are far in excess of what is recommended to prevent deficiency.

Vitamin A- 1000IU (recommended daily dose 50IU/kg, safe upper limit 2,099IU)
Vitamin C- 30mg (recommended daily dose 0, dogs and cats make their own)
Vitamin E- 5IU (recommended daily dose 1mg/kg)

These amounts are probably not high enough to cause harm, but given that most pets are fed diets already supplemented with more than enough of each, the amounts in this product are unnecessary as nutrients. The use of excess amounts of these vitamins as medicines to prevent or treat disease, is not proven, and has often turned out to do more harm than good when tried in humans.

As for the sprouted soybean meal, there is no scientific evidence to suggest health benefits from this either. The company sites a variety of epidemiological studies in humans indicating an association between eating tofu or other soybean food products and lower cholesterol levels, rates of some cancers, and a few other health problems. (They do not, of course, refer to any of the research in humans showing lack of benefit or potential risks from soy supplement products). All of this, unfortunately, is entirely irrelevant to whether or not this particular soy-based product has any benefits for dogs and cats.

The amino acids, vitamins, and minerals listed are all provided in adequate amounts in good quality commercial pet foods. The enzymes are of no benefit, particularly when taken orally since they themselves are destroyed by normal digestion. And none of the phytochemicals have yet been demonstrated to have any health benefits in dogs and cats. So while it is unlikely to be harmful, to is an expensive way to get a few nutrients your pet probably already has enough of and some chemicals that may or may not have any health effects, positive or negative. 

Black Leaf Tincture
This is an herbal product containing black walnut extract, olive leaf extract, and cayenne in 75% alcohol(!). The usual vague and unscientific claims are offered about supporting the immune system, the circulatory system, the digestive system, and so on.

Black Walnut- There is insufficient evidence to support any of the claimed health benefits despite traditional use for a wide range of unrelated problems. There is some concern about possible toxicity, from the walnut itself and from possible fungal contaminates.

Olive Leaf- The evidence in humans suggests some possible beneficial effects on blood pressure and cholesterol levels, but it is weak and not conclusive. There is no eveidence on the possible effects in dogs and cats.

Cayenne- There is a fairly large amount of preclinical research suggesting possible benefits in humans, but little in the way of clinical trial evidence, and nothing in dogs and cats. 

Probiotic
I’ve written extensively about probiotics, and this is an area in which I think some real benefits are possible. Unfortunately, we have yet to develop an adequate understanding of the normal gut ecology to be able to influence it in significant ways, and the evidence for real clinical benefits from specific products varies from weak to non-existent. Nzymes.com does nothing to change this. Their product contains a variety of typical probiotic bugs, and there have been no clinical trials to show that the specific combination has any value. The product was tested, however, in a study looking at quality and label accuracy for veterinary probiotics. It was found to contain only 2.7% of the number of bacteria claimed on the label, suggesting even the ingredient claims made for this product may be questionable, much less the claims of health benefits. 

“A Veterinary Study”
The company does claim to have one rather large veterinary clinical study from 1989 showing that dogs with musculoskeletal pain benefit from its sprouted soybean product. The study was never apparently published, and the information provided on the web site does not make it possible to evaluate it extensively. Six unnamed veterinarians apparently diagnosed dogs with “musculoskeletal inflammation” based on their own exams and the opinions of owners. They gave the supplement to 387 dogs, and 340 of them were reported as improved in one of more of these measures: energy, alertness, stamina, appetite, and accelerated healing. Most cases improved within the first week.

This is almost a cartoon caricature of what a scientific study shouldn’t be. No randomization, no placebo control group, no standardized diagnostic evaluation, no objective diagnostic evaluation (all subjective), no clearly defined diagnosis, no blinding, no record of other conditions or treatments used, and no predetermined or even halfway consistent criteria for response. Any high school science class ought to be able to put together a better “study.” If this is the best the company has been able to do in over 20 years, there is absolutely no reason to believe they have any interest in the scientific validity of their marketing claims. 

Bottom Line
These products are being marketed with an impressive number of the myths and warning signs of snake oil and pseudoscience. The theories offered for why these remedies should help your pet range from complete nonsense to vague unproven hypotheses. There is no scientific evidence to indicate any specific benefit from any of these products for any particular condition in dogs and cats. All the testimonials in the world can’t prove any of the company’s claims to be true, nor can they guarantee that the products cannot hurt your pets. Just as there is little evidence regarding the claimed benefits of these products, there is little to demonstrate that they are safe.

 

Posted in Herbs and Supplements | 247 Comments

Buyer Beware: How to Evaluate Pet Healthcare Products

This is a great time to be a pet owner. Advances in nutrition and veterinary medicine in the last few decades have led to tremendous improvement in the length and quality of our pets’ lives. We have more and better options for preventing and treating illness in our animal companions than ever before. And apart from professional medical care, there is a staggering variety of healthcare products available for our pets.

But there is a downside to this abundance of choices. We are stuck trying to figure out which products might help our pets, which might do nothing for them, and which might even be dangerous. The government does little to monitor the veterinary market or to require that individuals or companies selling products demonstrate they are safe and effective or that the marketing claims they make are true. And while veterinarians are often the best resource for information about how to care for our pets, they can’t know everything about all of the thousands of products pitched to pet owners. The primary responsibility for making smart choices for our pets lies with us.

Having investigated many of the nutritional supplements, herbal remedies, and other products claimed to benefit our pets’ health, I have developed a checklist that simplifies the process of evaluating unfamiliar pet care products. While this can’t replace a thorough, detailed investigation of a product and the evidence for claims made about it, this checklist can give you an idea of whether something is promising enough to be worth looking into in more detail 

  1. What is it?
  2. Does it make sense?
  3. What’s the evidence?
  4. Is it safe?
  5. Any Warning Signs?

What Is It?
The first question to ask when you hear about a healthcare product for your pet is, “What is it?” This means, what are the ingredients, how is it made, where does it come from, who discovered or invented it, how is it supposed to be used, and anything else that will help you understand what it is you are being asked to give or do to your pet. Certainly, the manufacturer of a pet health product should be eager to give you as much information as you want about what they are selling. If your questions are not answered, if the ingredients or processes are a secret, if you are offered a snowstorm of technical language and no one is willing to explain in plain English what the product is, that’s a reason to consider walking away right at the start.

Of course, you aren’t likely to get a balanced or complete picture about a product from someone selling it. It is important to look for other sources of information. While the information one finds on the Internet should always be taken with lots of grains of salt, it is copious and easy to find. A Google search can turn up lots of information. And when evaluating this information, consider the source. Veterinary medical schools, other scientific research institutions, organizations of medical specialists, and others not actively trying to make money from these products are likely to have more objective and balanced information about them 

Does It Make Sense?
This question is a bit more complicated than it seems, since lots of bad ideas seem reasonable, and a few good ones can sound crazy. This question is a way of getting at what scientists call plausibility and coherence. Basically, if the idea behind a product is a reasonable extension of what science already knows about health and consistent with established principles, then it is more likely to work than something which is based on some mysterious or magical process unknown to science and discovered by a lone genius with no medical training working in their garage. As Thomas Edison said, genius is 1% inspiration and 99% perspiration. Once in a while, a new idea springs up out of the blue and actually works. But most advances in medicine are hard won through careful, laborious building on what we already know.

It’s true, science can’t explain everything. But there are some things we can be pretty sure about. Did you know, for example, that scientists don’t really know exactly how gravity works? There are a couple of theories, and the details still aren’t totally worked out. But if someone offered you a magic collar that would let your dog fly, would you buy it? We may not know all there is to know about gravity, but we can be pretty darned sure it’s going to be there every time we jump out a second story window.

So when you read about a product for your pets that is based on a “revolutionary” new idea that scientists only doubt because they can’t understand it, or that works by some vague “energy” or “quantum” process that is exempt from the ordinary rules that govern the medicines or procedures your vet uses to help your pet, it is worth being a little skeptical and looking particularly closely at the answer to the next question, “What’s the evidence? 

What’s the Evidence?
A concept which has come to dominate human medicine, and which is gradually making progress in the veterinary field, is the idea of evidence-based medicine. People have long known that our individual experiences don’t give us a very reliable idea of what works and what doesn’t in protecting our own health. For thousands of years, basing our medical care on personal experience, tradition, and the words of respected and experienced doctors led to an amazing variety of useless, even dangerous treatments. Bloodletting, leeches, toxic “medicines” that poisoned rather than helped us, even ritual animal sacrifice were widespread therapies that patients and doctors believed worked based on their own experience. And yet most babies died before they could reach adulthood, and those that made it were lucky to reach their forties.

In the last couple of centuries, we’ve shifted the basis of our judgments about healthcare practices from experience to scientific research. The result has been an unprecedented level of success. From wiping out polio to dramatically reducing infant mortality to doubling average life expectancy, science has made our health better by relying on the best available research evidence rather than intuition, experience, history, or the wisdom of respected individuals.

Unfortunately, lots of products for our pets base their claims of success on nothing more than the reputations of inventors and celebrities or veterinarians who endorse the products, and the personal stories of satisfied customers. Unsatisfied customers are rarely heard from. And good quality scientific research is rare, especially when companies can make healthy profits selling their remedies without investing in efforts to prove they actually work. Likewise, it is easier to claim “thousands of years of success” than to carry out a good scientific study that actually proves the product works.

So when looking at the evidence for a product you’re considering giving to your pet, you have to look past the testimonials the manufacturer gives you. As emotionally compelling as stories of miraculous recoveries are, they are not a reliable guide to what works and what doesn’t. A trustworthy company interested in really helping your pet will be able to provide references t scientific studies published in reputable journals. Ideally, these will be studies of their actual product in the same species you are thinking about giving it to. Even evidence for some benefit from one of a dozen ingredients given to laboratory rats isn’t a very useful bit of evidence that the combination of all the components will help your dog or cat.

And as always, consider the source. The company can’t be expected to give you information against their own product, or to provide feedback from unhappy customers. So look for independent sources of information, ideally from medical professionals or otherwise with a scientific background able to access and evaluate the scientific evidence. 

Is it Safe?
There is no free lunch in medicine. If something has benefits, it has risks. If it has no possible risks, that means it doesn’t do anything at all. We cannot expect to tinker with as complex and interconnected a system as the physiology of a living organism and only generate the good effects we want. So any choice to give our pets a medicine or other product to protect or restore their health is always a choice that requires balancing potential benefits against potential risks. The more we know about the risks, the better we are able to make sound, informed decisions.

While companies can be expected to downplay the risks and hype the benefits of their products, a good one will admit that there are possible side effects and tell you what they are and about how often they happen. And again, this information is far more reliable if it comes from objective, scientific research rather than just the impressions of people who have tried the product. A list of possible side effects may be scary, but it doesn’t mean we shouldn’t use a treatment if we need to. At least if we know what side effects are possible, we can watch out for them. If we are told something is perfectly safe, we are being reassured at the cost of being totally in the dark about whether the product is safe for our pets. 

Are There Any Warning Signs?
There are a number of sources listing warning signs that should alert us to products which are likely scams or snake oils rather than real medicine for our pets. One of  my favorites is Dr. Walt’s Warning Signs of Quackery and Fraud. These cover some of the subjects I’ve already mentioned, and plenty of others. My own quick summary of the most important is this:

  1. If it sounds too good to be true, it probably is.
    I’ve already mentioned that anything with no possible side effects is probably too good to be true. The same goes for anything which promises nearly 100% success. Sure, maybe the company offers a “money back guarantee,” but realistically hardly anyone who doesn’t like the product is likely to go to the trouble to return it if it’s not extremely expensive, and when it comes to your pets’ health, getting your money back does little to make up for something that doesn’t work or hurts your companion.

This warning also applies to claims that a product can treat or prevent a wide range of unrelated disease or works to support or strengthen every system in the body. There is no single, simple cause for every illness, and there is no single, simple cure either. Anyone who tells you something, especially when they are selling something, is not giving you an honest or realistic picture.

  1. Mysteries, Miracles, and Magic
    We live in an imperfect world where we don’t know everything and we can’t fix or control everything. This leads to anxiety and a search for ways to make ourselves, and our pets, safer. Unfortunately, this also creates an opportunity for marketers to manipulate us by feeding us scary stories about potential health hazards and then offering to sell us something to protect our pets. When the advertising for a product makes claims about such hazards, or about something they offer to protect or restore your pets’ health, there are some red flags to watch out for.

If the claimed threat is dramatic, overly broad, or something your vet and mainstream science supposedly doesn’t know about or is trying to hide, this is a tipoff that it may be an exaggerated or even totally artificial threat, and that someone is playing on your fears to get to your wallet. And if the protection or remedy offered is a “revolutionary” new discovery (especially without any real scientific research behind it), or if it is claimed to be able to save almost any patient even when all other methods have failed, there is reason to be cautious.

Lots of complicated technical jargon isn’t necessarily a signs that there is real science behind the product. Good doctors will want you to be able to understand the disease they believe your pet has and the remedies they offer. Marketers often want to impress you without actually explaining anything. Advertising that clearly plays to your emotions but is short on facts and evidence is advertising to be wary of. The bottom line is that if you’re told something works miracles, that no one understands why, and that evidence beyond testimonials isn’t needed, you’re being given fairy tales, not evidence.

  1. Galileo and Dan Brown
    Galileo is best known today for being right about the earth orbiting the sun, and for being made to shut up about it by the religious authorities of the time who didn’t like the idea. He was undoubtedly an exceptional man in many ways, not the least of which is being right when most people thought he was wrong. While sometimes wild ideas that turn our understanding of the world upside down turn out to be true, the vast majority of the time they really are crazy and disappear into history without a trace.

Today, anyone with an implausible or radical idea is likely to answer criticism by comparing themselves to Galileo or the other exceptions in history, not the far more numerous misunderstood geniuses who were actually wrong. Claiming that the only reason an idea or product someone is selling you hasn’t been proven scientifically is because it’s too far ahead of its time and science can’t handle it is more likely to be a sign that you’re dealing with a great ego than with great genius.

Similarly, while I find the intricate conspiracies invented by Dan Brown in his novels, such as The DaVinci Code, very entertaining, I don’t find them very believable. When someone says that they don’t have science to back up their claims because veterinarians, pharmaceutical companies, pet food companies, the government, or a combination of these groups is actively suppressing the truth, they are telling stories more suited to fiction than reality. In particular, the suggestion that veterinarians would rather your pets be sick than healthy, so they can get paid to treat them, is absurd and offensive.

All of the steps on this checklist have to be considered together. An idea that makes sense and is consistent with well-established science can still be wrong, so considering the evidence is still necessary. And if an idea seems crazy but has lots of strong scientific research to back it up, it could very well be true (and it stands a good chance of winning a Nobel Prize, since the highest honors in science are given to those who reveal the errors of the past or break truly new ground).

It is always a good idea to consult your veterinarian if you have questions about a product or service affecting your pets’ health. Hopefully, they will be able to give you solid information to help evaluate the product, or at least to direct you to a reliable source where you could find this information. Veterinarians can’t be experts on everything, but the years they spend studying and working with pets are a resource you should take advantage of.

The frustrating reality is that the vast majority of products out there that claim to preserve or restore our pets’ health are based on guesses or unproven theories and have little in the way of hard evidence to tell us if they are safe or if they can do what they claim. One important rule in medicine is Primum Non Nocere, “First, Do No Harm.” There is ample evidence that unproven or unscientific remedies can be harmful, even if they claim to be safe. When the situation is desperate, and there is a great need to intervene and no well-established treatment available, it may be necessary to reach for something plausible even without strong evidence. But when the need isn’t so great, or when we are treating our own fears as much as our pets, we may be better off not gambling on a product that makes wild claims without hard facts behind them. And when there are well-studied and well-understood options with known risks and benefits, we are better off using these first, and saving the roll of the dice for later, or passing over it entirely.

In any case, as pet owners we are responsible for trying to make the most careful, rational, and best-informed choices possible when it comes to our pets’ health. Following this checklist will give you another tool to help you do this, and hopefully to keep your pets happy and well!

Posted in General | 5 Comments

Homemade Diets for Cats and Dogs with Kidney Disease–Most Recipes are Wrong

A new study has been published adding to the evidence, which I have discussed before(see articles listed below), that homemade diets are frequently nutritionally inappropriate and less consistent or reliable than commercial diets.

Larsen, JA. Parks, EM. Heinze, CR. Fascetti, AJ. Evaluation of recipes for home-prepared diets for dogs and cats with chronic kidney disease. Journal of the American Veterinary Medical Association. 2012;240(5):532-8.

The authors looked at 39 recipes from websites and published books for both veterinarians and pet owners (most written by veterinarians) and identified as intended for dogs with kidney disease and 28 such recipes intended for cats. Though the optimal amount and proportion of every possible nutrient is certainly not known for pets with kidney disease, there are some nutrients for which it is fairly clear that animals with kidney disease have different requirements from healthy animals. And the minimal amount of most nutrients needed to avoid deficiency (though not necessarily the optimal amount) is known for most nutrients. The authors systematically compared the nutrient profile of the recipes they examined with known minimal nutrient requirements and with the established special needs of cats and dogs with kidney disease.

Almost all recipes were vague about key ingredients, requiring the owner to guess about exactly what ingredient to use. Similarly, almost all recipes recommended some sort of nutritional supplement but did not offer specific guidance as to type, quantity, or nutrients. Some recipes offered clearly incorrect information, such as suggesting baking soda as a calcium source even though it contains no calcium.

The authors conclusions were:

None of the recipes assessed in the study reported here provided adequate concentrations of all essential nutrients…Furthermore, many recipes did not accommodate currently accepted nutritional strategies for managing [chronic kidney disease].

There is no doubt that homemade diets can be healthy and appropriate for dogs and cats, both those that are well and those with diseases requiring special nutrition. However, the case has not been made that home-prepared diets are superior to commercial diets, as is often claimed. And while commercial diets may not be optimal nutritionally for many individuals, they are at least consistent and monitored for minimal nutritional adequacy. Any benefits home-prepared diets might have won’t matter if they are grossly deficient or inappropriate in terms of essential nutrients.

For my own clients who wish to feed home-prepared diets, I always recommend consulting with a board-certified veterinary nutritionist (try the local veterinary medical school, or PetDiets.com) to ensure the diet is nutritionally appropriate for the individual pet. Recipes have been repeatedly shown not to be reliable, even when created by veterinarians, and relying on them is likely to lead to feeding a nutritionally inappropriate diet.

  1.     Freeman L, Michel K. Nutritional analysis of 5 types of “Raw Food Diets.” Journal of the American Veterinary Medical Association. 2001;218(5):705.
  2.     Lauten SD, Smith TM, Kirk CA, Bartges JW, Adams A, Wynn SG. Computer Analysis of Nutrient Sufficiency of Published Home-Cooked Diets for Dogs and Cats. Proceedings of the American College of Veterinary Internal Medicine Forum 2005.
  3.     Roudebush P, Cowell CS. Results of a hypoallergenic diet survey of veterinarians in North America with a nutritional evaluation of homemade diet prescriptions. Veterinary Dermatology 1992;3:23-28.
  4.     Taylor MB, Geiger DA, Saker KE, Larson MM. Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef. Journal of the American Veterinary Medical Association 2009;234(8):1041-8.

 

Posted in Nutrition | 31 Comments

Herbal Remedies Can Interfere with HIV Treatment

The popularity of herbal remedies rests, in large part, on the perceptions of these substances as “natural,” a vague, nearly meaningless term often mistakenly understood to mean “safe.” The idea that eating parts of plants, singly or in combination, can have significant health benefits with little to no risk is one of the irrational cornerstones of alternative medicine. On the other hand, the idea that plants contain compounds which can have both beneficial and adverse health effects is a well-established and generally accepted fact. Herbal remedies very likely do have health benefits, we simply rarely have the data to identify these or the associated risks with enough certainty to justify claims made for them or clinical use of them.

Despite this, such remedies are not infrequently used by patients, often without the knowledge or guidance of healthcare professionals. Exactly how popular herbals are is unclear, but individual surveys suggest a small but significant number of patients use them. I recently ran across one such study, which illustrates the use of herbal remedies by human HIV patients and also sheds some light on the attitudes of such patients and on the potential risks of this behavior.

Vazquez Hernandez, M. Hurtado Gmez, MF. Blanco, JR. The influence of alternative medicine in highly active antiretroviral treatment. Farmacia Hospitalaria 2009;33(1):31-6.

Highly active antiretroviral treatment (HAART) is an approach which significantly reduces HIV morbidity and mortality and improves the quality and length of patient’s lives. While not a cure or devoid of side effects, it is a highly effective treatment that has had a tremendously positive impact on the well-being of people infected with HIV. As with most incurable conditions, however, there is a subpopulation of patients who are interested in alternative therapies to replace or augment conventional care. This study found 16.6% of the HIV patients surveyed used 1 or more presumably medicinal plants.

37.5% of these people thought of these plants as a form of medication, which is the appropriate perspective to take on herbal remedies, apart from the lack of evidence to document safety and efficacy for many of them. However, another 37.5% of the patients did not know medicinal plants could have any side effects, and none of the patients realized that these agents could interfere with the HAART that was so vital to their health. 62.5% of the patients did not know what the herbal remedy they were taking was, could not say what it was for, and were taking it on the advice of someone who was not a healthcare professional.

A variety of herbal agents were used, with grapefruit, milk thistle, and Echinacea being the most common. Though information about safety and possible interactions with pharmaceuticals is extremely limited for most herbal products (no literature was found for 54% of the agents used), some published evidence of negative effects of HAART was seen for 46% of the agents reported, including the three most common ones. The authors concluded:

Patients undergoing HAART regularly use medicinal plants and this often occurs without the knowledge of the doctor or pharmacist. There is evidence that herbal preparations can cause pharmacokinetic and pharmacodynamic interactions that represent a potential risk in patients undergoing HAART…

The population in general and the patients perceive these substances as healthy. The patients are not aware of the adverse effects that these can sometimes produce and that they can even cause HAART to fail. The reasons given for the consumption of medicinal plants is that the patients believe that these increase the efficacy of their treatment, improve their quality of life, reduce the adverse effects of HAART and give them a feeling of control.

This is a summary which probably applies equally well to many of groups of patients. Herbal remedies with significant but poorly understood physiologic effects can impact, both positively and negatively, the health of people who take them, but most people know little about what they are taking or why, do not understand that the benefits are unclear and that there are possible risks, and most rely on the advice of people other than their primary healthcare team. If herbal remedies are to find a place as effective medicines, we need to develop the research base to understand their effects and we need to educate patients and healthcare professionals about the potential risks and benefits and interactions with other therapies. This, of course, requires debunking the fallacy that such products are inherently safe because they are “natural.”

Posted in Herbs and Supplements | 1 Comment

Veterinary Stem Cells and Snake Oil

I have written several articles previously about veterinary stem cell therapies, which I view as a promising but as yet unproven treatment for a number of medical problems. (e.g. 1, 2, 3, 4, 5)  Though not “alternative” in origin, the marketing of these treatments and the arguments used to justify them in advance of adequate scientific data establishing safety and efficacy resembles the promotion of many alternative therapies.

I have received some pretty harsh criticism for suggesting this, so it was satisfying to read a recent editorial in the journal Veterinary Surgery:

Jeffery ND. Is ‘Stem Cell Therapy’ Becoming 21st Century Snake Oil? Veterinary Surgery 41 (2012) 189–19.

The author begins by cautioning us against “a non-critical acceptance of new advances because of a complacent assumption that previous mistakes regarding poor medical regulation will not be repeated in the modern world.” Obviously, this blog exists precisely because such mistakes, and reliance on prescientific methods of evaluating new ideas through personal experience, uncontrolled experimentation, and trust in authority, rather than reliance on rigorous controlled scientific research, are still widespread in our profession. As Dr. Jeffery correctly points out, the majority of veterinarians rightly deride pseudoscientific methods such as homeopathy (though too many still fall for it’s propaganda). And yet the same approaches to justifying other kinds of clinical interventions, both conventional and alternative, are all too common.

He then goes on to remind us that the promising preclinical research involving stem cell therapies does not justify their widespread clinical use without properly designed and conducted clinical trials. Most research on these therapies published so far has been methodologically inadequate to justify the burgeoning market in stem cells. However, the uncritical reports in the media of preclinical research, and the easy availability of testimonials and uncontrolled anecdotes about stem cell treatment, not to mention the aggressive marketing by stem cell therapy companies, make it “easy to sell to owners as a respectable treatment, even in the absence of rigorous proof of efficacy.”

Finally, Dr. Jeffery emphasizes something with which I conclude most of my own articles about unproven therapies, a call for a stricter standard in veterinary medicine for scientific evidence about our interventions.

Whilst stem cell therapy has rapidly achieved high profile in medicine and therefore even misplaced claims for efficacy are noteworthy it is not the only therapy in veterinary medicine or surgery for which there is insufficient evidence of benefit to support widespread implementation. Novel interventions for common conditions are published frequently in veterinary journals, including Veterinary Surgery. Whilst it is undoubtedly important that new interventions are explained through publication, it is essential that they should subsequently be subject to critical testing of their effectiveness before being widely accepted. This is currently not standard practice in veterinary medicine and surgery… Strict testing of novel interventions must become the norm for veterinarians to be able to maintain our view of ourselves as a ‘science-led’ profession.

I couldn’t agree more.

Posted in General | 8 Comments

Garlic for Pets- What’s it Good for?

One of the most popular plant products touted for medicinal use in pets is garlic Allium sativum. A recent newsletter by Dr. Deva Khalsa, a popular alternative veterinarian, makes some typical claims:

Garlic is a miracle herb!

Garlic (Allium sativum) has been valued for thousands of years for medicinal purposes.

reported adverse affects from garlic add up to a total non-event over the past 22 years….This proves beyond the shadow of a doubt that the risk of using garlic is so infintessimally low that it’s simply statistically insignificant. What is significant is all the positive research delineating the medicinal powers of garlic.

a natural antibioitic

it’s antifungal, antiviral and antibacterial effects can contribute to the healing process.

Garlic increases general immune activity

Uncooked garlic helps to lower blood triglycerides and choleterol making it useful for certain breeds (Schnauzers and Beagles) that are predisposed to this problem.

Compounds in garlic act as antioxidants and help flush toxins out.

garlic has been fed to dogs in order to help prevent flea infestation.

A host of studies provide evidence that the allicin in garlic works to inhibit cancer formation.

Since these pretty fairly represent the claims made for garlic, I will address each in turn.

1. Garlic is a miracle herb-
Well, miracle is a pretty tough word to justify when applied to any medical therapy, all of which come with pros and cons. I’d call this a warning sign!

2. Garlic has been used medicinally for thousands of years.
True, but irrelevant to whether or not it works. The traditional use of plants as medicines has a poor record of predicting uses that are actually proven valid by controlled scientific testing. Here are some of the traditional uses record for garlic (from Wynn SG. Fougere BJ. (2007). Veterinary Herbal Medicine St. Louis: Mosby Elsevier.)

Traditionally, garlic has been used in humans [or animals] for abnormal growths, bronchitis, pneumonia, digestive problems, intestinal infection, tuberculosis, dysentery, earache and ear infection, vascular disorders…influenza…relieve toxicities, and kill parasites…treatment of a cow that was unable to rise after calving…coccidiosis in poultry…breast tumors on dogs (topically), for distemper, for jaundice, for rheumatism, and for thyroid complaints and worms…for fungal infection and swelling of the tongue, oral blisters and wounds…contagious abortion, tetanus, milky diarrhea, abdominal pain, asthma, polyuria, sores, compound fractures, epilepsy and swelling of the kidneys, gangrene of the lung…

When something is used to treat such a wide variety of apparently unrelated medical conditions, either it is a miracle or it is an example of how easily people can be fooled into thinking a useless therapy is helping. A truly miraculous therapy shouldn’t have any trouble proving itself in scientific testing, so when the evidence is lacking despite centuries of use and decades of research, the most likely explanation is human fallibility rather than miracle cure.

3. Risk of using garlic is negligible.
Mostly true. A number of in vitro and lab animal studies have shown the potential for garlic to cause anemia and other problems. Studies looking at garlic as a potential antimicrobial in swine feed found the pigs ate less and gained less weight (and also had and “objectionable” taste, for those carnivores among you). However, the amount of garlic which must be fed to cause clinical illness in dogs is probably much larger than is typically used. Cats are much more sensitive, but they are also less likely to accept garlic.

There are a couple of important caveats here, though. For one thing, the in vitro and lab animal studies showing potential dangers of garlic, which Dr. Deva and other proponents of garlic dismiss as not relevant to actual use, are exactly the same kinds of studies which show potential benefits and which they constantly cite to justify actual use of garlic. This is a classic case of confirmation bias in which people accept as valid evidence which supports their position but reject evidence which contradicts it.

The other factor is that there are case reports of individual dogs who experienced anemia, high blood pressure, and other serious adverse effects from consuming relatively small amounts of garlic (e.g. 1, 2). It is often the case with pharmaceuticals, which appear safe in relatively small test populations of a few thousand people, less common sensitivities in some individuals appear when they are given to much larger numbers of patients. This is part of the business of balancing the risks and benefits of any treatment. So while the risks of garlic appear to be low for most dogs, it is not appropriate to assume they are inconsequential, especially when evidence for benefits is so poor (as we will see).

4. Garlic has antibiotic, antifungal, and anti-parasitic properties.
Maybe. The basis of this claim, apart from low-reliability evidence such as anecdote and opinion, is in in vitro and animal model studies. Chemicals from garlic do have effects on bacteria, fungi, and parasitic organisms in the laboratory. This only suggests that these chemicals might have similar effects in the real world. It doesn’t prove anything. What an isolated chemical does in a petri dish is not necessarily what feeding garlic will do in a living animal. And as I often remind people, bleach has antibiotic, antifungal, and anti-parasitic properties in the lab, but I wouldn’t recommend it as a dietary supplement!

The research in real animals is mixed. Garlic has failed to show benefit in at least as many studies as it has shown some effects, so the balance of the evidence is unclear. And the published research is almost all in agricultural animals, not companion animals.

5. Garlic “boosts” the immune system.
Nonsense. The notion of a general immune stimulant which has clinically beneficial effects and no side effects is a fantasy that ignores the incredible complexity of the immune system and how it interacts with all the potential threats it is exposed to. This empty bit of marketing is discussed, and demolished, in detail in this article.

6. Garlic lowers triglycerides and cholesterol.
Probably not. A 2009 review of the research in humans found that “the available evidence from randomized controlled trial does not demonstrate any beneficial effects of garlic on serum cholesterol.” The point is largely moot since blood lipids are almost never a meaningful health issue in companion animal species. It is true, as Dr. Deva suggests, that it is an uncommon problem in certain breeds. However, I would note that both of the dogs in the case reports I mentioned before who suffered harm from eating garlic were Schnauzers, the same breed that most often exhibits this otherwise rare problem. So I’d be very careful about suggesting garlic as a remedy for this issue in this breed given the lack of evidence for a benefit and the presence of evidence for possible risk.

7. Garlic is an anti-oxidant and helps remove “toxins”
A hypothetical treatment for a hypothetical problem. First off, the subject of oxidation and anti-oxidants is about as complex as the subject of immune system activation, and there is growing evidence that anti-oxidant therapies do little good and some harm (e.g. 3, 4, 5). So while garlic compounds show some antioxidant properties in the lab, they also show the ability to cause oxidative damage (that’s where the anemia comes from), and there is zero evidence in real cats and dogs for any benefit from garlic as an anti-oxidant.

Secondly, the mysterious “toxins” so often mentioned as a target for health promoting therapies are a classic sign of snake oil marketing. Without information about specific toxins, evidence for the harm they do, information about how they are processed and eliminated by the body, and evidence concerning how garlic can aid in this process, this claim is totally meaningless. And, not surprisingly, none of the information or evidence is offered for garlic.

8. Garlic is an effective flea control method.
Doubtful. There are, of course, plenty of anecdotes from people saying that garlic drove the fleas away from their pets like magic. There are just as many that say garlic didn’t help at all. There is absolutely no research evidence showing garlic supplements to be an effective form of flea control. It is often given with Brewer’s yeast, which has been shown to be ineffective as a flea repellant. So for all the confidence with which this claim is made, it is simply made up.

9. Garlic is useful in prevention or treatment of cancer.
Maybe. There is low to medium level evidence in humans that eating garlic may reduce the risk of some kinds of cancer. The American Cancer Society concludes

there is not enough evidence at this time to support eating large amounts of garlic or taking garlic supplements for cancer prevention. Garlic may have the potential to interfere with anesthesia or other medicines. It is reasonable to include garlic as part of a balanced diet, unless one has a particular health problem or is taking medication that has been shown to be adversely affected by garlic.

Other research summaries show a mix of possible benefits and risks, including bleeding and interference with the action of a number of medicine. So like anything with the potential for benefit, there is the potential for harm.

And, as usual, none of this research has been done in companion animal species. So while extrapolation from research in humans is often necessary, it is also a great way to draw the wrong conclusions. Such research strongly suggests which ideas may be worth pursuing and which may not, but it certainly doesn’t provide a confident, reliable answer about what to do for our pets.

Bottom Line
In vitro and lab animal research suggests a number of potential uses for garlic. The same level of research suggests some potential danger to garlic use in dogs and cats. There is almost no clinical research to substantiate any of the claims made for garlic use in pets. Traditional use suggests almost every pant is a cure-all, and the majority of such claims have yet to pass the test of scientific study. So at this point, hysterical claims of garlic as a “miracle food” are totally unjustified. The potential benefits deserve to be investigated, but they are mostly theoretical and unproven. The risks are probably low overall, but some individuals have been harmed by eating garlic, and we are currently unable to predict accurately which patients will be adversely affected.

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