Nonsense on Stilts: How to tell science from bunk by Massimo Pigliucci

Massimo Pigliucci is an evolutionary biologist, philosopher, professor, and noted skeptic and author. He is also almost the same age as I am, but I’m trying not to let that ruin my day. His most recent book is Nonsense on Stilts: How to tell science from bunk.

There are many cogent arguments in this book which are relevant and useful for distinguishing between scientific and unscientific or pseudoscientific approaches to medicine, a major goal of this blog. In particular, I found Dr. Pigliucci’s response to postmodernist critiques of science and his discussion of the subject of expertise compelling and enlightening. There are also, however, many other subjects which are interesting in themselves but do not relate directly to the distinction between science and non-science. I began the book with the misapprehension, based on the title and some elements of the advertising and the introduction, that it was intended to be primarily about defining science and distinguishing it from non-science and especially from pseudoscience, which is what I take “bunk” to mean in this context. However, the books reads a bit more like a collection of loosely related essays than a structured argument. The back cover is only half right in that the subject matter is not really a “taxonomy of bunk,” as it is described, but it is an exploration of “the intersection of science and culture at large.”

I will briefly summarize the main points of each section of the book, partly to give a feel for its contents and also to point out those sections that relate to core issues this blog is concerned with. It should be taken as a given that the book itself is far more detailed and nuanced than my attempts to summarize, and that since much of it is well outside my own areas of expertise I may very well unintentionally misrepresent Dr. Pigliucci’s arguments. Since this review is more than long enough by itself, I intend to extract a few specific arguments from the book as subjects for separate posts.

Dr. Pigliucci begins by introducing the “demarcation problem,” the difficulty in distinguishing science from non-scientific or pseudoscientific approaches. He dismisses the popular notion, generally credited to Karl Popper, that science is distinguished primarily by falsifiability, that is one can tell a scientific explanation from a non-scientific one because the former contains criteria by which it can be disproved and the latter does not. I gather from the book that this idea is quite passé in the philosophy of science. But as Pigliucci points out, it is still quite popular among scientists and skeptics, so I would have appreciated a more thorough explanation of why it is inadequate before he moves on to alternative ways of understanding what science is.

The first chapter challenges the usual distinction between so-called “hard” sciences, such as physics, and “soft” sciences like psychology. Pigliucci contends that these two types of scientific endeavor are not really distinguished by the quality, precision, or accuracy of their data but by the degree to which they are predictive or historical. The branches of science usually understood as “hard” are very good at measurement and prediction within controlled conditions but weaker at accounting for more complex “real world” events. The historical sciences, by contrast, can often convincingly explain past events but are not every effective at prediction.

I’m not entirely convinced by this characterization, nor do I see exactly how it leads to what seems to be the main conclusion of this chapter, which is that both approaches deserve the label “science” because they share “the ability to produce and test hypotheses based on systematically collected empirical data (via experiments or observations.)” He returns to this definition in his conclusions, where he defines science this way:

…an investigation of nature, based on the construction of empirically verifiable theories and hypotheses. These three elements, naturalism, theory, and empiricism are what make science different from any other human activity.

This seems a pretty reasonable approach to characterizing science as an intellectual and social endeavor. I’m not entirely sure that the book clearly and logically builds up to this definition, so it seems to appear a bit mysteriously at the beginning and the end and in several places between. This may be my own lack of sophistication in following Dr. Pigliucci’s arguments, but again my impression is that the book is an interesting but meandering stroll through issues associated with science and other elements of culture rather than a forceful linear argument leading up to a final conclusion about what is and is not science.

The next chapter gives several examples of “almost science,” areas of theorizing and research which Dr. Pigliucci doesn’t feel reach the level of full science. The main subjects he uses as examples are string theory and the multiple worlds interpretation of quantum mechanics, the Search for Extraterrestrial Intelligence (SETI), and evolutionary psychology. The first apparently fails the test of empiricism in that the hypotheses these theories generate are not yet testable. SETI is characterized as not entirely scientific because it appears not to be falsifiable (negative findings are expected most of the time, so while a single positive finding would justify the endeavor, no number of negative findings could prove the whole thing a waste of time) and because its theoretical foundations are judged weak. Evolutionary psychology as applied to humans is judged insufficiently testable to be solidly scientific, though it may be true science when applied to species which can be observed and manipulated sufficiently to validate or falsify specific hypotheses.

It is clear that Dr. Pigliucci is taking great pains to avoid an overly simplistic application of his defining criteria. He repeatedly reminds the reader that these “almost sciences” are not equivalent to outright pseudosciences like astrology and creationism. Yet there seems to be a degree of subtlety and subjectivity to his assessments that make the value of the whole category of “almost science” a bit questionable. If there are sufficient shades of gray between (almost) universally accepted “real” science on the one hand and (almost) universally accepted non-science on the other, than some significant segment of the continuum in between simply cannot be reliably assessed as science or not science. This may be the intrinsic nature of messy reality, but if our goal is to distinguish science from non-science for important practical reasons, too much nuance and ambiguity undermine that goal.

This is similar to the problem of the reliability of scientific conclusions. It is true, of course, that scientific truths are inherently probabilistic and provisional. But it is also true that once a certain degree of confidence in an idea can be justified by sufficient evidence, doubting such an idea becomes irrational and skepticism becomes willful denialism. In trying to avoid an overly simplistic and rigid set of criteria and in recognizing the inevitable uncertainties in all knowledge, I think Pigliucci sometimes is too careful and undermines the utility of his own, quite reasonable and otherwise useful approach to defining science.

In the next chapter, Dr. Pigliucci discusses several examples of pseudoscience, included HIV/AIDS denialism, astrology, UFOs, and the investigation of paranormal phenomena. While he does a variable job of illustrating why the specific examples are untrue (dissecting astrology in detail but talking mostly about the consequences rather than the factual falsity of AIDS denialism), and he covers many of the usual reasons why people believe in pseudoscience, he doesn’t really use these examples to illustrate a general thesis or approach to identifying pseudoscience and distinguishing it from science.

The next several chapters are interesting in themselves, though  again they really read as a loosely connected set of essays on the relationship between science and society. He discusses how the media (mis)portrays science and scientific information, he talks about the character of the public intellectual and its role in society, he discussed science and politics through the climate change debate, and he looks at the relationship of science and the courts through the example of the intelligent design movement.

There then follows a brief history, in two chapters, of the development of those elements of philosophy that relate to, and eventually become, science. I found this section fascinating, and I enjoyed seeing the development of core ideas underlying modern science portrayed as a historical narrative.

The next three chapters are by far my favorites, and they deal with the subject of expertise, and with the complex but critical issue, from the point of view of science-based medicine, of how we acknowledge the limitations of science and guard against them while at the same time not abandoning science and reason altogether and simply accepting a faith-based approach to knowledge or an epistemologically nihilistic approach like that of extreme postmodernism that says no knowledge is possible. I will be examining Pigliucci’s arguments and conclusions in detail in a future post, because I think he very effectively addresses these issues and points the way to a reconciliation and synthesis that is very useful.

Though I began Dr. Pigliucci’s book with a bit of a misconception of what he was setting out to accomplish, and consequently found only a few sections of it directly applicable to my interest in understanding the distinction between science and non-science, I still found the book interesting and informative. His prose is quite readable, even when dealing with complex issues. I might have preferred a bit less qualification in some areas, but I respect his efforts to present complex and nuanced issues honestly and without oversimplification. Overall, I certainly recommend Nonsense on Stilts.

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UK National Health Service Report on Dietary Supplements

I just wanted to draw a little attention to an excellent report just published by the UK National Health Service on dietary supplements for humans.

Supplements: Who Needs Them

This is an excellent, readable summary of the evidence concerning the most common dietary supplements for humans. Covered are:

Multivitamins
Fish Oil
Glucosamine
Echinacea
Zinc for Colds
Weight Loss Supplements
Body Building Supplements
Gingko
Ginseng
Supplements for Aging

Posted in Herbs and Supplements | 2 Comments

Study on Glucosamine for Feline Interstitial Cystitis Does not Suggest any Benefit

A recent research study performed in Thailand has been reported in the American Journal of Veterinary Research (AJVR) which addresses the possibility that oral glucosamine might be useful for treating Feline Interstitial Cystitis (FIC).

Panchaphanpong J, Asawakarn T, Pusoonthornthum R. Effects of oral administration of N-acetyl-d-glucosamine on plasma and urine concentrations of glycosaminoglycans in cats with idiopathic cystitis. Am J Vet Res. 2011 Jun;72(6):843-50.

FIC is a poorly understood condition in which cats experience many of the symptoms of a bladder infection, including blood in their urine and straining to urinate, and which can even lead to urinary tract obstruction in males. For years, such cats were assumed to have bacterial urinary tract infections (UTIs) and treated with antibiotics. Since most were given a 7-10 days course of antibiotics and most got better within that period, it was long believed that the treatment was working and was confirmation of the diagnosis of UTI. This is a classic example of how misleading clinical experience and the post hoc ergo propter hoc fallacy can be. Eventually, controlled scientific research revealed that the condition is usually inflammatory, not infectious, and typically resolves on its own. Antibiotics don’t help, and since they can cause vomiting, diarrhea, loss of appetite, or wounds on the hands of the person trying to give them to a cat, they are actually more likely to do harm than to help these patients.

Because glycosoaminoglycans (GAGs), like glucosamine, are a normal part of the protective lining of the bladder wall, it has been hypothesized that supplementing with GAGs might be useful in preventing or treating this condition. This paper, however, doesn’t provide much support for that hypothesis.

The study was double-blinded and placebo controlled w/ randomization. There were only 19 cats with FIC (7 in the placebo group and 12 in the glucosamine group), and 10 normal cats were used as controls. The authors gave the treatment group glucosamine (and the placebo group an identical placebo) for 28 days. Blood and urine samples were obtained (though not always from every subject) on the first day before treatment and then at 7, 14, 21, 28, and 56 days after the start of the study. Treatment was discontinued at 28 days.

There were no bloodwork abnormalities in any of the normal or FIC cats. The only difference in urine test results was in the presence of blood in the urine. Before treatment, 6/12 (50%) of the treatment group had no blood in their urine, and at the end of treatment 10/12 (83%) cats in the treatment group were without blood in their urine. In the placebo group, 1/7 (14%) were free of blood before treatment and 5/7 (70%) had no blood in the urine at the end of the 28 days. The authors suggest that because a higher percentage of the treatment group were free of blood in the urine at the end, this suggests the treatment reduced this symptom of FIC. However, no statistical analysis was done to determine if the difference between 83% and 70% is significant, which it may well not be in so small a sample. And a much higher percentage of the placebo group had blood in their urine to begin with, so if anything this group seemed to have a greater improvement over the course of the study than the cats receiving glucosamine.\

Another variable measured was the concentration of GAG in the blood and urine. If GAGs are going to be useful as an oral medication, they have to be absorbed and reached therapeutic levels in the tissue where the problem is. In this study, blood levels of GAG did increase significantly in the treatment group at Days 21 and 28. GAG levels were greater in the treatment group than the placebo group at Day 21, but not at Day 28. And the starting GAG levels in the blood were the same for the normal control cats and for those with FIC. So while it seems the oral glucosamine did increase the blood level of GAG somewhat, it is not clear that blood levels are related to the presence of FIC or that the increase was meaningful since it was not consistently present but only seen at one out of four measurement times.

Another variable measured in the study was the level of GAGs in the urine. Urine GAG levels at the start of the study were higher in cats with FIC than in normal cats. The authors suggest this may be the result of GAG leakage from the inflamed bladder wall in cats with FIC. Urine GAG levels in cats treated with glucosamine were significantly higher than that of cats in the placebo group at only one of the four measurement times, Day 14. The authors imply that this might be a sign of the oral glucosamine reaching the bladder, a necessary prerequisite for the glucosamine having any potential medicinal use for this condition. However, as mentioned the difference only existed at one time point. And if it is true that the FIC cats had higher urine GAG levels than the normal cats at the start of the study because this was a symptom of their diseases, then why are higher levels later interpreted as a potentially positive sign rather than as an indication of greater inflammation and leakage from the bladder wall?

This was a well-designed and conducted study which, as so often happens, was interpreted in a more positive way than really justified by the data reported. Overall, it is consistent with previous studies which suggest that oral glucosamine is probably absorbed to some extent, though it may or may not reach physiologically meaningful concentrations in blood or other tissues. However, there is little indication that the supplement had any significant impact on the FIC affected cats. No clear, consistent effect on clinical symptoms or laboratory measures was observed. The study is useful in investigating in a systematic and generally objective way the potential for oral glucosamine as a therapy for FIC, and by and large it does not suggest there is much value in glucosamine as an FIC therapy.

Posted in Herbs and Supplements | 3 Comments

Alternative and Complementary Therapies for Cancer: Recent Studies find Danger and no Benefits

There are different ways to employ alternative medical therapies. Sometimes they are used in place of conventional, scientific medicine. More commonly, they are used along with conventional therapy and simply given the credit for any improvement. However, in either case there is frequently little or no research data to show whether or not such therapies are beneficial or harmful. A couple of recent studies addressing this issue have appeared which found no benefit to so-called integrative use of CAM therapies and significant harm to the replacement of conventional cancer treatment with these alternative approaches.

Han E, Johnson N, Delamelena T, Glissmeyer M, Steinbock K. Alternative therapy used as primary treatment for breast cancer negatively impacts outcomes. Ann Surg Oncol 2011;Jan 12 [Epub ahead of print].

The first study looked at 61 patients with treatable breast cancer who either declined or delayed conventional therapy in favor of alternative approaches. The mortality was significantly increased and the success of treatment greatly decreased in these patients. Those who declined conventional therapy altogether did especially poorly.

Judson P, Dickson E, Xiong Y, Peterson J, Geller M, Ghebre R et al. A prospective, randomized trial of complementary/alternative medicine for women with ovarian cancer [Abstracts Presented for the 41st Annual Meeting of the Society of Gynecologic Oncologists, Annual Meeting of the Society of Gynecologic Oncologists]. Gynecol Oncol 2010; 116(S2):S142-S143.

The second study looked at 43 women with ovarian cancer who were treated with chemotherapy alone or chemotherapy with hypnosis, healing touch, and massage. No differences in objective measures nor in quality of life were found between the standard care and the “integrative” care groups.

Obviously, these studies only involved a limited number of patients with particular conditions and particular CAM approaches, so they cannot be viewed as anything like a definitive statement on the value, if any, of alternative therapies alone or in combination with conventional cancer treatment. However, these alternatives are often marketed with confident pronouncements about their value that go well beyond any claims that could be justified by the available evidence. If CAM proponents wish to see their therapies used as replacements for conventional treatment or even as adjuncts to it, the onus is on them to demonstrate the safety and the benefits of such approaches.

These studies clearly do not support the use of these therapies, particularly when substituted for established treatments. Instead they show that there is a great danger in replacing treatments with known risks and benefits with treatments that have not demonstrated their worth, and that we cannot simply assume that even benign therapies like massage will necessarily benefit patients with cancer.

Posted in General | 1 Comment

Salmonella and Other Risks of Raw Pet Diets

Primal Pet Foods, a popular marketer of commercial raw diets for dogs and cats, recently announced a recall of one of its raw cat foods because testing has suggested the diet may be contaminated with the bacteria Salmonella. Such recalls in the pet food industry are typically precautionary, and most of the time no actual harm results for pets or their owners. Nevertheless, since advocates of homemade and raw diets tend to promote such recalls as evidence of the unhealthy nature of conventional commercial pet diets, and to try and equate every recall with the tragic, but unusual, melamine contamination problem of 2007, I feel it is important to point out that raw diet and other pet products touted as “natural” and healthy are also subject to such recalls.

Whether or not this particular diet turns out to be source of disease for pets or their owners is less important than the general health risks posed by raw pet diets. I have discussed these diets at length before (e.g. here and here), and the bottom line is this:

1) The theoretical arguments used to promote them are not sound.

2) There is no evidence for the supposed health benefits claimed for raw diets or for most of the health hazards raw diet advocates claim are associated with conventional pet foods.

3) The risks of raw diets are probably small but certainly greater than those for conventional foods, without any apparent benefits to justify them.

These conclusions are much the same as those in a research review being presented next week at the annual meeting of the American College of Veterinary Internal Medicine. Dr. Anread Fascetti, a board-certified veterinary internist and nutritionist, reviews the literature concerning raw diets (1), and finds a number of serious concerns.

A. Nutritional Inadequacy:
A number of studies of both commercial and homemade raw diets have found significant nutritional deficiencies or excesses (2, 3). In one study, cats fed a diet based on raw rabbits developed heart muscle disease associated with a deficiency of the amino acid taurine (4).

B. Lack of Health Benefits:
The little research that has been done on raw diets does not support dramatic claims of health benefits. Some research has found subjective differences in coat and stool quality but not in any other factors evaluated (4). One study suggested that periodontal disease was reduced by adding oxtail to the diet, but other studies have found high rates of periodontal disease in wild dogs and feral cats consuming whole prey (5, 6), and no difference in oral health between domestic cats eating commercial diets or mostly whole prey (7).

C. Health Risks:
As I have pointed out before, raw diets are more likely than cooked diets to be contaminated with infectious organisms, including Salmonella. Such organisms have been found in raw diets (1, 8-12) and have been found shed in the feces of pets eating these diets (13), they can be passed from pets to humans (13-16), and they have caused illness in both pets and humans (16-18).

Another recent paper in the Journal of the American Veterinary Medical Association, written by Dr. Kate KuKanich (19), specifically addresses the subject of Salmonella contamination in pet foods and treats. Her analysis of the literature shows that uncooked foods and treats are far more likely to be contaminated with Salmonella, and that up to 69% of sled dogs and 61% of racing greyhounds fed raw meat shed this organism in their feces even when they have no diarrhea or other clinical symptoms. This is compared to a rate of shedding of less than 5% up to 15% in studies of other healthy dogs. While Salmonella contamination after cooking has been found in dry diets, the risks for uncooked foods and treats are substantially higher, and Dr. KuKanich concludes, as I would,

Ample evidence exists for the risk of Salmonella contamination in raw food diets; thus, it is advised that pet owners avoid feeding raw food diets to pets.

 

References
1. Fascetti AJ. Raw food diets: A research review. Proceedings, American College of Veterinary Internal Medicine Forum, Denver, CO, June 15-18, 2011.

2. Freeman L., Michel, K., Nutritional analysis of 5 types of “Raw Food Diets.”  JAVMA March, 2001;218(5): 705.

3. Dillitzer, N, Becker, N, Kienzle, E. Frequency and extent of nutritional imbalances in “bone and Raw food” (barf) rations. Proceedings Waltham Interational Nutritional Sciences Symposium, Cambridge, UK, September 16-18, 2010. p. 44.

4. Glasgow AG, et. al. Role of Diet in the Health of the Feline Intestinal Tract And in Inflammatory Bowel Disease. Center for Companion Animal Health, School of Veterinary Medicine, University of California at Davis. Accessed June 5, 2011 at http://www.vetmed.ucdavis.edu/ccah/local-assets/pdfs/Role_of_diet_feline%20health_Glasgow.pdf

5. Steenkamp G, Gorrel C. Oral and dental conditions in adult African wild dog skulls: a preliminary report. Journal of  Veterinary Dentistry. 1999 Jun;16(2):65-8.

6. Verstraete FJ, van Aarde RJ, Nieuwoudt BA, Mauer E, Kass PH. The dental pathology of feral cats on Marion Island, part II: periodontitis, external odontoclastic resorption lesions and mandibular thickening. Journal of Comparative Pathology. 1996 Oct;115(3):283-97.

7. Clarke DE, Cameron A. Relationship between diet, dental calculus and periodontal disease in domestic and feral cats in Australia. Australian Veterinary Journal. 1998 Oct;76(10):690-3.

8. Chengappa MM, Staats J, Oberst RD, Gabbert NH, McVey S. Prevalence of Salmonella in raw meat used in diets of racing greyhounds. Journal of Veterinary Diagnostic Investigations. 1993 Jul;5(3):372-7.

9. Joffe DJ, Schlesinger DP. Preliminary assessment of the risk of Salmonella infection in dogs fed raw chicken diets. Canadian Veterinary Journal. 2002 Jun;43(6):441-2.

10. Weese JS, Rousseau J, Arroyo L. Bacteriological evaluation of commercial canine and feline raw diets. Canadian Veterinary Journal. 2005 Jun;46(6):513-6.

11. Morley PS, Strohmeyer RA, Tankson JD, Hyatt DR, Dargatz DA, Fedorka-Cray PJ. Evaluation of the association between feeding raw meat and Salmonella enterica infections at a Greyhound breeding facility. Journal of the American Veterinary Medical Association. 2006 May 15;228(10):1524-32.

12. Leonard EK, Pearl DL, Finley RL, Janecko N, Peregrine AS, Reid-Smith RJ, Weese JS. Evaluation of pet-related management factors and the risk of Salmonella spp. carriage in pet dogs from volunteer households in Ontario (2005-2006). Zoonoses Public Health. 2011 Mar;58(2):140-9. doi: 10.1111/j.1863-2378.2009.01320.x.

13. Finley, R. et al. The risk of Salmonella shedding by dogs fed Salmonella-contaminated commercial raw food diets. Canadian Veterinary Journal. 2007;8:69-75.

14. Gutman LT, Ottesen EA, Quan TJ, Noce PS, Katz SL. An inter-familial outbreak of Yersinia enterocolitica enteritis. New England Journal of Medicine. 1973 Jun 28;288(26):1372-7.

15. Morse EV, Duncan MA, Estep DA, Riggs WA, Blackburn BO. Canine salmonellosis: A review and report of dog to child transmission of Salmonella enteritidis. American Journal of Public Health. 1976 Jan;66(1):82-4.

16. CDC. Outbreaks of multidrug-resistant Salmonella Typhimurium associated with veterinary facilities—Idaho, Minnesota, and Washington, 1999. MMWR Morbidity and Mortality Weekly Report 2001;50:701–704.

17. Canadian Communicable Disease Report. Human health risk from exposure to natural dog treats. 200(26).41. Acessed June 5, 2011 at http://www.collectionscanada.gc.ca/webarchives/20071217102424/http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/00vol26/dr2606ea.html

18. Finley R, Reid-Smith R, Weese JS. Human health implications of Salmonella-contaminated natural pet treats and raw pet food. Clin Infect Dis. 2006 Mar 1;42(5):686-91. Epub 2006 Jan 20.

19. KuKanich KS. Update on Salmonella spp contamination of pet food, treats, and nutritional products and safe feeding recommendations. Journal of the American Veterinary Medical Association 2011 Jun;238(11):1430-1434.

Posted in Nutrition | 11 Comments

From The Daily Mash: Made-up Medicine Works on Made-up Illnesses

A spot of British humour with your tea? Here are few excerpts from the article

Made-up medicine works on made-up illnesses

ACUPUNCTURE has been shown to be extremely effective amongst people who have nothing wrong with them.

Experts stressed that acupuncture, like murder and lying, has existed for thousands of years and works on the fundamental Chinese principle that if it hurts it must be working.

Professor Henry Brubaker, of the Institute for Studies, said: “To truly assess the efficacy of acupuncture a widespread double-blind test needs to be conducted over a series of years but to be honest it’s the equivalent of mapping the DNA of pixies or conducting a geological study of Narnia.”

Posted in Humor | 2 Comments

Evaluation of the Chinese Herbal Remedies San Ren Tang, Wei Lin Tang, and Alisma for Feline Urinary Tract Disease

Though herbal remedies often have an aura of being somehow fundamentally different from drugs used as medicines, they are really just collections of chemical compounds. As such, they ought to be evaluated just as conventional pharmaceuticals are: identification and isolation of active compounds, in vitro experiments establishing potential beneficial and harmful effects, in vivo studies looking at absorption, metabolism, and safety, and finally well-controlled clinical trials escalating in size and complexity to determine safety and effectiveness in the target species and disease conditions. There is no reason such remedies cannot be effective therapies, but there is also no reason to assume they are safe or effective without following these steps. For a variety of practical and philosophical reasons, unfortunately, many potentially useful herbal products are not properly tested, and their use is based on much less reliable foundations, such as folk tradition and personal experience.

Therefore, I always appreciate it when I see important and necessary, though often not glamorous, preclinical research on such remedies. This kind of research can be invaluable in guiding us towards or away from specific remedies, though it is only one piece of the puzzle and cannot definitively confirm or refute the potential usefulness of specific herbal products. An abstract being presented at the upcoming American College of Veterinary Internal Medicine Forum presents the data from just such a laboratory study.

M. Daniels; J.W. Bartges; D.M. Raditic; C.A. Kirk; A. Callens; S. Marsden; G. Galyon
Evaluation of 3 Herbal Compounds Used for Management of Lower Urinary Tract Disease in Cats

The study evaluated three herbal products to see if they increased urine volume or changed the chemical constitution of the urine in was believed to reduce the risk of Feline Lower Urinary Tract Disease (FLUTD), a common and uncomfortable condition in cats. 6 healthy cats were used in the study, and they were randomly assigned to be given each of three products or a placebo in turn: San Ren Tang, Wei Ling Tang, and Alisma. A 24-hour urine sample was collected and analyzed after 2 weeks of treatment with each product for each cat. None of the products showed a significant difference from the placebo in any variable measured.

I am not familiar with the basis on which these products are recommended for FLUTD, so I cannot evaluate the plausibility of the underlying theory. However, the products are herbal remedies within the Traditional Chinese Medicine (TCM) approach, and I have already discussed elsewhere the principles of TCM and why they are fundamentally inconsistent with a scientific approach to medicine. Individual herbal products undoubtedly have active chemical compounds, both from the plant ingredients and often deliberate or accidental contaminants, but without proper scientific evaluation there is no valid way to designate specific products as treatments for specific conditions or to evaluate their safety and efficacy.

This study was not intended, of course, to definitively answer the question of whether these herbal preparations are safe or beneficial for cats with FLUTD. The particular urine characteristics measured are known to play a role in the risk of developing FLUTD symptoms, but there are other risk factors, and the precise steps leading to the condition in individual cats are not clearly understood. So these products could conceivably be beneficial even if they do not influence the variables looked at in this study. However, given the apparent lack of a sound scientific rationale for using them, and the lack of a plausible mechanism or established preclinical effects, such remedies cannot be routinely recommended. And given the limited resources available for research into new veterinary therapies, it seems it would be most efficient to focus those resources on therapies that seem promising on the basis of established scientific knowledge, rather than the far less reliable criteria of traditional use. Studies on herbal remedies should, therefore, focus on developing this important preclinical knowledge before proceeding with clinical trials.

Posted in Herbs and Supplements | 16 Comments

Azodyl for Kidney Failure in Cats: An Update on the Evidence

In a recent article about pet supplements for the Science-Based Medicine Blog, I reviewed the dietary supplement Azodyl, marketed for kidney failure in dogs and cats. At the time, the evidence I was able to find was extremely limited, poorly controlled, and subject to a high risk of bias due to association of the research with the company marketing the products. My conclusion was that the theory behind the product was weakly plausible and the evidence insufficient to justify a firm conclusion about efficacy.

An abstract is being presented at the upcoming American College of Veterinary Internal Medicine Forum which reports the results of a controlled study on the use of this product in 10 cats with  chronic kidney disease.

M. Rishniw; S. Wynn
Azodyl Fails to Reduce Azotemia in Cats with Chronic Kidney Disease (CKD) When Sprinkled Onto Food 

The study examined whether there was any difference between commonly measured blood markers of kidney disease, blood urea nitrogen (BUN) and creatinine, in cats given Azodyl and cats given a placebo. The Azodyl was sprinkled on the food since this is commonly how the product is used (making cats take capsules is often difficult). The study was randomized, double blinded, and placebo controlled. The criteria for confirming a positive effect were quite generous, however no difference was found between cats given Azodyl and cats given the palcebo.

The authors concluded:

Based on these results, Azodyl, applied by sprinkling onto food fails to reduce [BUN and creatinin] in cats with [chronic kidney disease]. Whether intact capsule administration reduces reduces azotemia in cats with [chronic kidney disease] remains unknown.

Though generally well-designed, this study was small, and of course single studies are almost never sufficient to provide the final word on a particular therapy. The issue of potential bias for or against a hypothesis is always hard to evaluate objectively, but I am unaware of any direct funding or other involvement of the company in this study. I do know that one of the authors, Dr. Susan Wynn, is a prominent researcher and advocate in the area of herbal and some other alternative therapies, so she certainly would not be expected to have a bias against the product. And negative findings in clinical research are inherently more reliable than positive findings because our studies and our psychology are designed to confirm our beliefs rather than refute them. So while the case is by no means closed, the balance of the very limited evidence is currently against any significant clinical value for this product.

Posted in Herbs and Supplements | 132 Comments

Veterinary Homotoxicology

What Is It?
Proponents of homotoxicology (also sometimes known as “complex homeopathy”) present it as an advancement or improvement in homeopathy, one that is more scientific and compatible with conventional medicine than classical homeopathy. It can more accurately be seen as a faction or sect that has split off from mainstream homeopathy with quite different, but equally unscientific, theories about the cause and treatment of disease.

Like classical homeopathy, made up by Samuel Hahnemann in the 19th century, homotoxicology was largely invented by one man, a German homeopath named Hans-Heinrich Reckeweg. Just as Hahnemann created many of the founding principles of homeopathy without regard to contemporary or modern scientific principles, so Reckeweg apparently invented the fundamental principles of homotoxicology. These principles continue to be assumed true by practitioners of homotoxicology, with all subsequent elaboration of the theoretical and practical aspects of the approached being based on these unproven, and implausible ideas.

The core concept of homotoxicology is the “discovery” of yet another One True Cause of all illness. Reckeweg decided that all illness is a manifestation of the body’s struggle to eliminate toxins. As he put it,

According to homotoxicology, all of those processes, syndromes, and manifestations, which we designate as disease, are the expression thereof that the body is combating poisons and that it wants to neutralize and excrete these poisons. The body either wins or loses the fight thereby. Those processes, which we designate as disease, are always biological, that is natural teleological processes, which serve [as] poison defense and detoxification.

Reckeweg went on to describe an elaborate model of stages of detoxification, each with characteristic symptoms, and an encyclopedic list of treatments for particular symptoms dictated by this model.

This is a variation of a popular notion among purveyors of alternative medicine, that disease can be attributed largely to “toxins” and that “detoxification” is the goal of healthcare. The notion is appealing because our innate emotional mechanism of disgust prime us to view things in our environment with certain physical characteristics (strong smells in particular) and things associated with illness, as potentially harmful. To this we add the notion of contagion, a category of sympathetic magic, which suggests that such things can harm us even when distanced from their source. These intuitive concepts make us susceptible to the idea that the symptoms we have and diseases we experience are the result of exposure to contagious, toxic substances. “Miasmas,” “bad air,” and many other vague sources of contagion have been posited as the cause of illness in periods or cultures without a detailed scientific understanding of the mechanisms of common illnesses.

At first glance, these ideas make some sense. There are, of course, infectious and toxic substances in nature which can make us ill. And prior to the development of a scientific understanding of the mechanisms of infection and poisoning, the general tendency to avoid anything which triggered our disgust mechanisms or which was associated with illness in some way was a reasonable precaution. However, this logical foundation cannot support the elaborate and fanciful structures built on it by those who promote the general principles of “toxins” as the cause of all disease. The fact that toxins and infectious organisms cause some disease does not logically mean that they cause all disease, nor does it lend any legitimacy to the proposed methods of “detoxification” often promoted. The kind of vague and mythologized notion of “toxins” behind homotoxicology and other “detoxifying” therapies has no legitimate scientific basis.

The model and practices of homotoxicology overall are a prime example of a pseudoscience, and the marketing of this approach includes many warning signs associated with pseudoscientific therapies. Abundant scientific terminology is employed, often with no clear, specific meaning or recognizable association with how such terminology is used by conventional science. All kinds of things are labeled as toxins, including infectious organisms, true toxic chemicals, substances assumed but not proven to be harmful, and the normal products of metabolism. No rigorous effort is made to demonstrate the assumed relationship between specific substances, the body’s mechanisms for eliminating them, and the course of particular diseases. All of this is simply accepted based on Reckweg’s initial insight and the personal experience of subsequent practitioners of homotoxicology.

Likewise, the choice of remedies for the presumed consequences of the body’s struggle to eliminate toxins is not based on any rational, scientific foundation. While practitioners often accept conventional diagnoses and monitor their patients with the usual tests, the scientific understanding of the conditions treated is not involved in selecting or applying therapy. The remedies used are mostly homeopathic, though they are sometimes made and applied in ways contrary to the principles and standards of classical homeopathy. Remedies are combined rather than given singly, they are often given by injection rather than orally, and they are often less extensively diluted than many homeopathic products.

The instructional materials produced by the company Reckweg founded, Heel Inc., explain in exhaustive detail the use of particular remedies for many conditions. However,  the links between the conditions as defined in conventional medicine, the theories invented by Reckweg, and the particular products Heel makes are not made in these materials or elsewhere. There is a lot of smoke and mirrors, including extensive use of technical scientific language and references to in vitro research and basic biology and chemistry not directly related to the methods or claims of homotoxicology. But no clear, direct, consistent, or convincing evidence is provided to support the use of particular remedies for particular medical conditions, only a few in vitro studies showing some possible effects of some preparations.

Because some remedies used in homotoxicology are not ultradilute homeopathic preparations, it is possible that they contain biologically active compounds. These products may be a bit more like herbal remedies than true homeopathic remedies. However, as with herbal remedies, the presence of potentially active chemical compounds doesn’t by itself indicate safety or effectiveness. A plausible mechanism, in vitro and in vivo evidence of bioavailability and measurable effects, evidence concerning side effects, clinical trial evidence of safety and efficacy, and reliable standards for quality control are all necessary to demonstrate a treatment is beneficial and appropriate for general use.  

Does It Work?
There is little reliable published research in humans on the clinical application of homotoxicology. A systematic review of the scientific literature found 7 trials with methodologically sound design, of which 6 reported positive results. No two trials looked at the same condition, so there was no replication to demonstrate a consistent, repeatable benefit. There was also a considerable risk of bias which was not controlled for in these studies. Almost half included authors who worked for the company making the remedies studied, and others were funded by this company or published in the Journal of Biomedical Therapy, a publication specifically created by the company to promote its approach and products. Often these potential sources of bias were not disclosed by the authors of the studies.

It is well-established that industry-funded research is more likely to show  positive results than independently funded studies regardless of the honest intentions of investigators. It is also clear that negative results are less likely to be published than positive results and industry created journals are untrustworthy marketing organs, not real scientific journals. Such sources of bias are loudly and justly identified when the products of the conventional pharmaceutical industry are at issue. Yet proponents of alternative medicine often seem willing to overlook them when discussing the products of dietary supplement, herbal remedy, or homeopathic remedy manufacturers. In the absence of the strict government oversight that is applied to the pharmaceutical trials, the limited and likely biased evidence produced by proponents and manufacturers of homotoxicology products is simply not reliable.

It is also worth noting that Heel Inc. (under a variety of names) has repeatedly been sanctioned by the Food and Drug Administration for violating the laws and regulations governing the marketing of homeopathic medications. From 1984 through 2005, the FDA has issued multiple warning letters and attempted to ban importation of Heel products due to illegal marketing claims. This sort of behavior further undermines the validity of the limited and already questionable research and marketing information this company supplies. The unfortunate reality is that the manufacturer of these remedies is the main source of information about the safety and efficacy of their own products, which is a far worse example of the fox guarding the henhouse than even the case of the conventional pharmaceutical industry.

Few veterinary studies of homotoxicology methods or remedies have been published. Unsurprisingly, uncontrolled case reports from proponents claim significant benefits. A published study of one Heel Inc. product for arthritis in dogs also claimed a positive result, but close analysis of the study identifies a number of methodological problems and questionable manipulations of the data, though at least there did not appear to be a significant issue of industry influence in this study as in most of the research in humans.

Overall, there is insufficient clinical trial data to clearly establish the effectiveness of homotoxicology treatments for any particular condition. This does not, of course, prove such treatments are not effective, but in consideration of the implausible theories, lack of cogent preclinical evidence, and abundant evidence against effectiveness for classical homeopathic remedies, this lack of evidence does call for significant skepticism. The existing evidence clearly does not justify the confident claims of benefit made by advocates of this approach.

Is It Safe?
I am not aware of any reports of direct harm from homotoxicology treatment. For hose remedies which are ultradilute and contain no active ingredients, as is the case for classical homeopathic remedies, there is clearly no risk of direct injury. Since some products used in complex homeopathy may contain active compounds, however, there may some risk of adverse effects, drug interactions, and allergic reactions.

The absence of any evidence of harm is not really a positive sign in one sense, since it is almost certainly evidence of the absence of any real effect. Side effects don’t occur because “drugs” are bad but because any treatment that has a measurable effect on one part of a complex living system will certainly have other, unintended effects on other parts of that system. If there are no possible risks, there can be no possible benefits.  The key to evaluating the safety of a medical therapy is to balance risks and benefits, and though the risk of direct harm is probably little to none for these products, there is also little evidence of any benefit.

Of course, there is certainly risk of indirect harm if homotoxicology is used in lieu of established medical treatments. Many people have been harmed in this way by classical homeopathy. It appears that Heel Inc. and many practitioners of homotoxicology do not recommend their treatments as replacements for conventional therapy, but as adjuncts or as treatment for conditions in which conventional therapy has not been successful. Though it is not at all clear that such uses add any benefit, it seems unlikely that they do any harm.

Bottom Line
The theoretical foundation of homotoxicology, that all disease is an expression of the body’s fight against toxins, is not scientifically valid. The remedies used are predominantly homeopathic, and while the ultradilute ingredients are highly unlikely to have any biological effects, there may be active chemical compounds in the less dilute preparations. There is no consistent, reliable preclinical research validating the potential effectiveness of most remedies used in this approach, though isolated studies show some in vitro effects for some preparations. The limited clinical research in humans is mostly associated with a major marketer of homotoxicology remedies and so is at high risk of bias. The even more limited veterinary research is weak and unconvincing. Additional clinical research does not seem justified until the validity of the implausible theoretical foundations of homotoxicology is established through preclinical study. There does not seem to be a significant risk of harm from homotoxicology treatment so long as it is not used in lieu of established therapies.

Posted in General, Homeopathy | 3 Comments

Sleights of Mind: What the Neuroscience of Magic Reveals about our Everyday Deceptions

The first step in accepting the need for skepticism and a systematic, scientific approach to evaluating medical therapies is understanding the limitations of our perceptions and judgments. Human beings all share innate and inescapable blind spots, both sensory and cognitive, that leave us vulnerable to misconceptions. And unfortunately, our sense of certainty about what we know is not a reliable guide to whether we are actually correct in our beliefs.

So I have a fascination for neuroscience in general, and especially the study of how our brains generate our perceptions, beliefs, and misconceptions. I was recently given a brilliant book on this subject which I thought might be of interest to some readers even though it is not specifically about the subject of medicine. Sleights of Mind: What the Neuroscience of Magic Reveals about our Everyday Deceptions by Stephen Macknik and Susana Martinez-Conde.

The authors are neuroscientists who specialize in the way the brain handles vision. As experts on visual processing, they are especially familiar with the ways in which our visual sense can misrepresent the world, and can be fooled by skilled manipulators of perceptions such as magicians. Both authors are founding board members of the Neural Correlate Society, which hosts the annual Best Illusion of the Year contest.

However, in Sleights of Mind, the authors go well beyond the subject of optical illusions. They illustrate, through the performance art of magic, how we can be fooled by others and, most often, how we fool ourselves, due to a variety of neural mechanisms involving all the sense as well as “higher” functions such cognition, memory, expectation, and the illusion of free will.

Through examples and demonstrations by world-class magicians, Drs. Macknik and Martinez-Conde show us how consistently and dramatically we can be mislead even when we are warned in advance that a magician intends to fool us. And while they only occasionally refer specifically to how these sensory and cognitive blind spots lead us to false beliefs about healthcare, the applicability to medicine is quite clear. We are often wrong when we subjectively or informally evaluate a medical therapy because of the same blind spots that lead us to be easily fooled by magicians and con artists. And while not perfect, carefully controlled clinical research is far less susceptible to such errors and thus a more reliable foundation for judgments about the causes of disease and our treatment interventions.

The authors include many of the illustrations of the blind spots they discussion on their web site. From simple visual illusions to seemingly impossible failures of perception (such as the failure to notice clowns and people in gorilla suits standing right in front of you when your attention has been effectively directed elsewhere), these demonstrations should give us all cause for a healthy skepticism about our own judgment and beliefs. And the best part is that the process of seeing our weaknesses exposed is still entertaining and fun! I highly recommend Sleights of Mind not only because, as a skeptic, I think “it’s good for you” but also because it’s fun.

Posted in Book Reviews | 4 Comments