New Study on Raw Diets for Dogs Adds Little to Ongoing Debate

Posted on July 3, 2012 by skeptvet

I am always on the lookout for research studies concerning raw diets for dogs and cats. A lot of claims are made about the health benefits of raw diets, but there is no substantive body of evidence to justify these claims. In particular, claims that raw diets are healthier than commercial dry or canned pet foods are common, despite no clinical studies making this comparison. I hope eventually such studies will be done, and while I am skeptical raw diets will prove superior, I will be happy to start recommending them if they prove to have benefits that outweigh their risks.

Unfortunately, a recent study of raw diets doesn’t add much information directly relevant to the debate.

Beloshapka, AN. et al. Effects of inulin or yeast cell-wall extract on nutrient digestibility, fecal fermentative end-product concentrations, and blood metabolite concentrations in adult dogs fed raw meat-based diets. American Journal of Veterinary Research 2012;73(12):1016-1023.

The study compared raw beef and chicken-based diets with or without a couple of prebiotics (not probiotics) in research dogs. All dogs were fed each of the diets, and measurements were made of body weight, fecal consistency, nutrient digestibility, and fecal chemicals associated with the presence of prebiotics.  

The short version of the results is:

  • The diets were highly digestible (though previous studies have suggested commercial and cooked fresh diets are also highly digestible, and no clinically significant effects on health have been shown to be associated with any differences in the digestibility of these different forms of pet food.
  • Over the three weeks of time on each diet, all of the dogs remained healthy on all of the diets.
  • The beef-based diet varied more than expected from the predicted nutrient composition, likely due to variation in the nutrient profile of individual ingredients. This is a big problem for homemade diets generally, which are not nutritionally consistent and aren’t monitored for any nutrient excesses or deficiencies on an ongoing basis as commercial diets are.
  • Fecal consistency (but not amount) varied with diet composition, but feces were normal for all dogs on all diets.
  • Fecal volume was lower than previously reported for dry commercial diets, though again the relevance of this for health hasn’t been established. Given the risks of raw diets, feeding them just to have less poop to pick up doesn’t seem sensible.
  • The prebiotics increased the levels of certain compounds in feces, as they have previously been shown to do. This is hypothesized to have health effects, but these have not been demonstrated.
  • Skin and coat quality did not appear to be affected by diet.
  • Interestingly, the mean urine specific gravity on all of these diets was greater than 1.046 for all diets. This is highly concentrated urine for dogs, suggesting potentially inadequate fluid intake. Interestingly, another study from the same institution, one comparing fresh cooked and raw diets with dry kibble in cats, also found unusually concentrated urine, and no difference between raw/fresh and dry diets. This certainly isn’t consistent with the claims that one benefit of raw diets is greater moisture content and less work for the kidneys. 

It is not clear from this report whether or not the diets were formulated to be nutritionally adequate as defined by AAFCO standards, though levels of calcium and phosphorus were reported to be within acceptable limits (though variable based on the specific ingredients in each of the diets). Obviously, nutritional adequacy would be an important issue in evaluating the quality of any diet.

So overall, this study shows that raw diets are highly digestible (which is not surprising, but of questionable importance), that short-term feeding of them under controlled circumstances doesn’t seem to have any negative effects or any benefits unless one considers less poop an important benefit or buys into the still unproven health benefits of prebiotics. There is nothing wrong with studying the variables this project looked at, of course, but it doesn’t have much direct bearing on the controversy over feeding dogs and cats raw diets.

Posted in Nutrition | 6 Comments

FDA Finds Widespread and Serious Violations of Safety and Quality Control Regulations for Dietary Supplements

Posted on July 2, 2012 by skeptvet

Despite the possibility that some dietary supplements could have real health benefits, there are many reasons to be skeptical of the safety and value of most supplements on the market. Most have not been tested scientifically to an extent that marketing claims made about them are truly legitimate. Unfortunately the legal framework for regulating these products almost guarantees that most never will be adequately tested. Thanks to the politicking that has led to the Dietary Supplement Health and Education Act (DSHEA), this “travesty of a mockery of a sham” masquerading as public health regulation makes it possible for the multibillion dollar industry that is Big Supplement to profit from selling supplements without ever having to prove they do what the companies claims, so long as the claims are sufficiently vague and the Quack Miranda Warning is appended I small print at the bottom of the page. As a consequence, the supplement industry can make a sizeable sum of money without having to turn around and invest much of that in research or quality control.

The supplement industry is known to spend a far smaller share of its profits on research that the larger, and much more closely watched, pharmaceutical industry, since the law requires little evidence of safety and efficacy for its products. However, even DSHEA requires some minimal quality control standards for herbal remedies and dietary supplements as well as placing some limits on the marketing claims that can be made. The GAO has previously reported that, despite this, contamination with dangerous substances and illegal marketing practices are common in the herbal medicine industry.

And now FDA inspection reports have shown that the dietary supplement industry also has serious and widespread problems with quality control, safety, and regulatory compliance.

The Chicago Tribune has published an article detailing the failings of the supplement industry to meet even its minimal obligations under DSHEA. Here are some examples: 

  • The FDA has found violations in nearly half of the 450 firms it has inspected.
  • 1 in 4 supplement companies have been issued a formal warning letter for violations, a significant enforcement action under the limitations placed on FDA by DSHEA.
  • Violations of good manufacturing practices were found in nearly two-thirds of 204 inspections conducted this year alone.
  • About 1 in 4 products the company tests have a significant problem, said Tod Cooperman, president of ConsumerLab.com. Some contain significantly less of an ingredient than is promised on the label, some far more. Sometimes the product contains contaminants, like lead. Some are rancid. Some have the correct ingredients but are “bedpan bullets” — incorrectly formulated pills that won’t break up in the body.

There is a huge body of evidence showing that inadequately tested supplements and an insufficiently regulated supplement industry can not only fail to help but can actively harm people (see below). And the limited evidence from the veterinary field is certainly no better than that for the human supplement market.

There is a dangerous double standard that requires chemicals called drugs to be extensively and expensively tested (which isn’t always sufficient to prevent harm even with great efforts) and yet chemicals called “herbs” or “supplements” can essentially avoid any testing of safety or efficacy. Even attempts to require basic accuracy in labeling, quality control in manufacturing, or honesty in advertising are routinely ignored by this industry. Without more serious efforts to control the supplement companies, people will continue to waste their money, and even sometimes damage their health, by using these unproven and uncontrolled products. 

Some of the Harm Caused by Vitamins, Supplements, and Herbal Remedies
Vitamin C can interfere with chemotherapy.

Vitamin E can increase cancer risk

.Vitamin E not useful for prevention for prostate cancer and can increase risk of congestive heart failure.

Vitamin E supplements increase risk of hemorrhagic stroke

Vitamin E supplements may increase risk of heart attacks and stroke

Vitamin E increases risk of prostate cancer

Vitamin supplements may associated with overall increase in mortality and no benefit in preventing gastrointestinal cancer.

Omega-3 Fatty Acids may increase risk in ventilator patients with acute lung injury

Mursu J, et al. Dietary supplements and mortality rate in older women: The Iowa Women’s Health Study. Archives of Internal Medicine. 2011;17(18):1625-33.

Widespread Failures in Quality Control of Dietary Supplements Herbal Preparations, Including Ayurvedic and Traditional Chinese Medicine (TCM) Herbs:

Aliye Uc, MD, Warren P. Bishop, MD, and Kathleen D. Sanders, MD, Camphor hepatoxicity. South Med J 93(6):596-598, 2000,

Angers RC, Seward TS, Napier D, Green M, Hoover E, Spraker T, O’Rourke K, Balachandran A, Telling GC. Chronic wasting disease prions in elk antler velvet. Emerg Infect Dis. 2009 May;15(5):696-703.

Angkana R, Lurslurcharchai L, Halm E, Xiu-Min L, Leventhal H, et al. Use of herbal remedies and adherence to inhaled corticosteroids among inner-city asthmatic patients. Annal Allerg Asthma Immunol 2010:104(2);132-138.

Berberine. Inbaraj JJ, Kukielczak BM, Bilski P, Sandvik SL, Chignell CF. Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) Chem Res Toxicol 2001 Nov;14(11):1529-34

Booth JN 3rd, McGwin G. The association between self-reported cataracts and St. John’s Wort. Curr Eye Res. 2009 Oct;34(10):863-6.

Burkhard PR, Burkhardt K, Haenggeli CA, Landis T.Plant-induced seizures: reappearance of an old problem. J Neurol 1999 Aug;246(8):667-70

Chung-Hsin Chen,Kathleen G. Dickman,Masaaki Moriya, Jiri Zavadil, Viktoriya S. Sidorenko, Karen L. Edwards,Dmitri V. Gnatenko, Lin Wu, Robert J. Turesky, Xue-Ru Wu, Yeong-Shiau Pu, Arthur P. Grollman. Aristolochic acid-associated urothelial cancer in Taiwan. Proceedings National Academy of Sciences, April 2012.

Panax ginseng: A Systematic Review of Adverse Effects and Drug Interactions. Drug Saf 2002;25(5):323-44 Drug Saf 2002;25(5):323-44

Cupp MJ Herbal remedies: adverse effects and drug interactions. Am Fam Physician 1999 Mar 1;59(5):1239-45

Debelle FD, Vanherweghem JL, Nortier JL.Aristolochic acid nephropathy: a worldwide problem. Kidney Int. 2008 Jul;74(2):158-69. Epub 2008 Apr 16.

Emery DP, Corban JG Camphor toxicity. J Paediatr Child Health 1999 Feb;35(1):105-6

Ernst E Adverse effects of herbal drugs in dermatology. Br J Dermatol 2000 Nov;143(5):923-

Fugh-Berman A Herb-drug interactions. Lancet 2000 Jan 8;355(9198):134-8

Huang WF, Wen KC, Hsiao ML. Adulteration by synthetic therapeutic substances of traditional Chinese medicines in Taiwan. J Clin Pharmacol. 1997 Apr;37(4):344-50

Kutz GD. Herbal dietary supplements: Examples of Deceptive or questionable marketing practices and potentially dangerous advice. General Accounting Office. May 26, 2010.

Lai MN, Lai JN, Chen PC, Tseng WL, Chen YY, Hwang JS, Wang JD. Increased risks of chronic kidney disease associated with prescribed Chinese herbal products suspected to contain aristolochic acid. Nephrology (Carlton). 2009 Apr;14(2):227-34.

Lawrence JD. Potentiation of warfarin by dong quai. Page RL 2nd, Pharmacotherapy 1999 Jul;19(7):870-6

Means C. Selected herbal hazards.Vet Clin North Am Small Anim Pract 2002 Mar;32(2):367-82

Nizsly N, Grizlak B, Zimmerman M, Wallace R. Dietary Supplement Polypharmacy: An Unrecognized Public Health Problem? eCAM 2010 7(1):107-113

Norred CL, Finlayson CA Hemorrhage after the preoperative use of complementary and alternative medicines. AANA J 2000 Jun;68(3):217-20

O’Connor A, Horsley CA. Yates, KM “Herbal Ecstasy”: a case series of adverse reactions. N Z Med J 2000 Jul 28;113(1114):315-7

Pittler MH. Ernst, E Risks associated with herbal medicinal products. Wien Med Wochenschr 2002;152(7-8):183-9

Poppenga RH.Risks associated with the use of herbs and other dietary supplements. Vet Clin North Am Equine Pract. 2001 Dec;17(3):455-77, vi-vii

Pies R Adverse neuropsychiatric reactions to herbal and over-the-counter “antidepressants”. J Clin Psychiatry 2000 Nov;61(11):815-20

Prakash S, Hernandez GT, Dujaili I, Bhalla V. Lead poisoning from an Ayurvedic herbal medicine in a patient with chronic kidney disease. Nat Rev Nephrol. 2009 May;5(5):297-300.

Raman P, Patino LC, Nair MG. Evaluation of metal and microbial contamination in botanical supplements. J Agric Food Chem. 2004 Dec 29;52(26):7822-7

Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G Acute heart transplant rejection due to Saint John’s wort. Lancet 2000 Feb 12;355(9203):548-9
Saper RB, Phillips RS, Sehgal A, Khouri N, Davis RB, Paquin J, Thuppil V, Kales SN. Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet.JAMA. 2008 Aug 27;300(8):915-23.

Shad JA, Chinn CG, Brann OS Acute hepatitis after ingestion of herbs. South Med J 1999 Nov;92(11):1095-7

Smolinske SC J Am Med Womens Assoc 1999 Fall;54(4):191-2Dietary supplement-drug interactions.

Tachjian A, Maria V, Jahangir A. Use of herbal products and potential interactions in patients with cardiovascular disease. J. Am. Coll. Cardiol. 2010 55: A32

Wang JD, Lo TC, Chen PC. Increased mortality risk for cancers of the kidney and other urinary organs among Chinese herbalists. J Epidemiol. 2009;19(1):17-23. Epub 2009 Jan 22.

Zhang SY, Robertson D. A study of tea tree oil ototoxicity. Audiol Neurootol 2000 Mar-Apr;5(2):64-8

Kidney failure from aristolochia in TCM herbals preparations.Lead, mercury and arsenic in herbal preparations.

Lead in TCM preparations.

Lead in ayurvedic preparations.

Lead in herbal preparations.

Tea Tree Oil Can be toxic to cats.

Toxic metals in Brazilian herbal preparations.

Contamination of herbal products with undisclosed pharmaceuticals.

Widespread contamination of supplements with undisclosed toxins and parmaceuticals

Unpredictable levels of coumarin in cinnamon bark, even within the same tree, pose risk of liver damage

 

Posted in Herbs and Supplements, Law, Regulation, and Politics | 2 Comments

Dowsing and Homeopathy: Using Magic to Test Magic

Posted on June 29, 2012 by skeptvet

Like the subject of pet psychics, the subject of dowsing is one I never thought it would be necessary to write about. This form of divination, like casting rune stones or knuckle bones and examining the entrails of sacrificial animals, is so clearly superstitious nonsense incompatible with science that it is hard to imagine even the most extreme advocates of alternative medicine taking it seriously.

Sadly, my ability to imagine the credulity of others has proven insufficient. A recent article in the Journal of the Royal Society of Medicine has chosen to treat dowsing, as employed by practitioners of another bit of folk magic, homeopathy, as a proper subject for serious scientific inquiry. (The paper is in the April issue, so I still secretly hope it was intended as an April Fool’s joke)

R McCarney, P Fisher, F Spink, G Flint, R van Haselen. Can homeopaths detect homeopathic medicines by dowsing? A randomized, double-blind, placebo-controlled trial. J R Soc Med 2002;95(4):189-191.

The authors describe dowsing this way.

Dowsing is a method of problem-solving that uses a motor automatism, amplified through a pendulum or similar device. In a homeopathic context, it is used as an aid to prescribing and as a tool to identify miasm or toxin load….Dowsing, also known as divining, water witching or rhabdomancy, has been defined as a ‘problem solving technique which apparently utilizes a motor automatism in conjunction with a mechanical instrument to obtain information otherwise unknown to the dowser’

I prefer this definition, from the Skeptic’s Dictionary:

Dowsing is the action of a person–called the dowser–using a rod, stick or other device–called a dowsing rod, dowsing stick, doodlebug (when used to locate oil), or divining rod–to locate such things as underground water, hidden metal, buried treasure, oil, lost persons or golf balls, etc. Since dowsing is not based upon any known scientific or empirical laws or forces of nature, it should be considered a type of divination and an example of magical thinking.

The authors of the dowsing study list several theories for how dowsing “works:”

Theories on dowsing come into three categories. Normal inference theory suggests that the dowser processes a large amount of information pertinent to the scenario at a subconscious level and moves the instrument accordingly. The physical theory sees the movement in the device being due to the amplification of minute reactions in the human body, with the precise nature of the reaction being unclear. It could be an electromagnetic field, or some form of vibrational energy.

According to the theory of psionic medicine, every living thing and inanimate object is continuously vibrating at a molecular level. This vibration is sensed subconsciously by the dowser, and it is then amplified through the pendulum or other dowsing device. Some proponents of this explanation suggest that this sense originally developed as a survival tool because it enabled individuals to find water. As the vibrational pattern can change with disease, it is purported to be a useful tool for clinical practice.

Finally there is the psychical theory which suggests the dowser employs some form of extrasensory perception.

They have, however, omitted one very important theory:

The ideomotor effect refers to the influence of suggestion or expectation on involuntary and unconscious motor behavior. The movement of pointers on Ouija boards, of a facilitator’s hands in facilitated communication, of hands and arms in applied kinesiology, and of some behaviors attributed to hypnotic suggestion, are due to ideomotor action… The term “ideomotor action” was coined by William B. Carpenter in 1852 in his explanation for the movements of rods and pendulums by dowsers, and some table turning or lifting by spirit mediums (the ones that weren’t accomplished by cheating). Carpenter argued that muscular movement can be initiated by the mind independently of volition or emotions. We may not be aware of it, but suggestions can be made to the mind by others or by observations. Those suggestions can influence the mind and affect motor behavior.

In other words, dowsing is yet another example of people fooling themselves into believing that outside forces are accomplishing actions which, in fact, they are generating through their own unconscious need to see what they want and expect to see.

Dowsing has been studied a number of times, in as scientific a way as it is possible to study magic. The studies have pretty consistently shown that with any reasonable controls for bias (such as blinding of the dowsers), dowsing doesn’t work. Dowsers have not demonstrated the ability to find anything with an accuracy better than chance if they don’t know in advance where it is.

Naturally, dowsers often complain that this failure is due to the effects of the testing situation, which in some undefinable way muddies the psychic waters so they can’t perform. In the current study, this concern was accommodated.

In discussions before the study began, dowsers expressed concern that the pressure of an experimental situation might be detrimental to the dowsing sense. For this reason the study packs were mailed to the volunteers for evaluation in their own time in relaxed conditions…there was generally a high level of confidence in the responses (n=99, 63.5%), which suggests that we were successful in making the dowsers feel relaxed about the study.

So how was the study conducted? Well, six registered homeopaths with experience in the medical applications of dowsing were sent 26 pairs of unlabeled bottles containing either a homeopathic solution (a 12C preparation of Bryonia which, as the authors put it, “is ‘ultramolecular’…a dilution of 10-24…very unlikely to contain any molecule of the starting material”) and a placebo (prepared in an identical way except from distilled water instead of the Bryonia mother tincture).

In other words, they received two bottles of water one with magic powers and one without. They also received a pair of labeled bottles to practice on. They were then instructed to identify the magic water (I mean the homeopathic remedy) by magic (I mean dowsing).

And how did they do? Of 156 selections between pairs of bottles,

48.1% responded correctly (n=156; 95% confidence interval 40.2%, 56.0%; P=0.689)….percentage of correct responses ranged from 34.6% (n=26; 95% CI 15.77%, 53.4%; P=0.170) to 61.5% (n=26; 95% CI 42.4%, 80.6%; P=0.327). Of responses given with high confidence, 45.0% were correct (n=99; 95% CI 35.6%, 55.3%; P=0.421).

So, almost eerily close to perfect chance levels, with performance no better for those who were confident in their choices versus those who knew they were guessing. In fact, “High confidence was slightly more associated with an incorrect response.”

Since this is science, the authors made some comments about the potentially inappropriate application of statistics (using a method which assumes independent samples for samples that are actually associated), but as they put it,

The data were in fact so far from showing any type of effect of dowsing that the assumption of independence was probably met, so the more appropriate clustered analysis is unlikely to show a different effect.

So does this close the book on “medical dowsing?” Undoubtedly not. It does serve, however, as an excellent illustration of the premise of this blog. The application of scientific study to the highly implausible only seems justifiable if resources are unlimited or if the results, when negative, will influence peoples belief in implausible practices. Neither of these conditions is met in the real world.

In an ideal world, it might make sense to study every idea no matter how unlikely to be truth based on established knowledge, since once in a great while crazy ideas actually turn out to be right. But in the real world, they usually don’t. Since we have to conserve our resources and use them as efficiently as possible in investigating potential therapies, and since scientific evidence against magic does little to reduce people’s belief in magic, conducting and publishing studies like this seems a pointless and unconscionable waste of time and effort which only conveys an inappropriate sense of legitimacy to the hypotheses being studied. On the other hand, it is entertaining.

Posted in Homeopathy | 9 Comments

New Survey: What Do Vets Think About Evidence-Based Medicine?

Posted on June 24, 2012 by skeptvet

A couple of years ago, I conducted a small pilot survey of veterinarians to investigate their attitudes and knowledge concerning evidence-based medicine (EBM). While not a representative sample of the profession, the survey identified some interesting issues worthy of further investigation. While respondents were generally very positive about the idea of evidence-based medicine, they generally had little knowledge or training in EBM methods. Many practitioners felt that research information was potentially useful in general practice but was overwhelming in quantity and difficult to access of interpret in an efficient, timely manner. A recent qualitative survey of decision-making processes used by veterinarians in Belgium also found that few were applying EBM methods to their clinical practice.

Vandeweerd JM, Vandeweerd S, Gustin C, Keesemaecker G, Cambier C, Clegg P, Saegerman C, Reda A, Perrenoud P, Gustin P. Understanding veterinary practitioners’ decision-making process: implications for veterinary medical education. J Vet Med Educ. 2012 Summer;39(2):142-51.

Over two-hundred veterinarians were interviewed by telephone, and a small number (31) were interviewed in person. The authors major conclusions were these:

First, veterinarians in this population were far from applying the principles of EBM…The results of this study showed that the EBM approach (asking questions, searching the literature, critically appraising the internal validity of the identified publications, assessing the external validity of the scientific information) was rarely used to inform decisions.

In this study, veterinarians preferred colleagues, the Internet, and textbooks to peer-reviewed journals and literature searches.

This study suggests that veterinarians also use two modalities of decision making: either by (1) recognizing the similarity to a past situation or (2) choosing the most likely solution among a list of possible options, sometimes excluding options in a hypothetico-deductive approach, sometimes proceeding by trial and error.

The study also identified several pragmatic factors that strongly influenced veterinarians’ decision-making. One was time. Veterinarians reported the perception that clinical decisions must generally be made quickly, and that the time needed to employ EBM methods might be incompatible with the demands of private practice.

Another factor was the perception that a methodical, rigorous scientific approach might not satisfy clients. As the authors reported, “[Respondents] perceived that owners want to see immediate action, which does not allow any delay in decision making; as one participant stated, ‘If I am called, it is to give an answer to the owner. It is not possible to say or do nothing, even if you are not sure. Owners request an action.”

Such concerns about the time required to make proper use of scientific research results in formulating decisions and the perceived antipathy of owners to delay or uncertainty are certainly real issues veterinarians must face. Unfortunately, they can easily lead away from a rational, thoughtful science-based approach to clinical decision making and favor a more reflexive, automatic, and opinion-based strategy, which is less likely to lead to the best results.

The study authors make a number of reasonable suggestions for improving the usefulness of EBM to veterinarians. The obvious first step is to improve the quantity and quality of scientific research information in the field. Then it is necessary to make this information available to ordinary practitioners in a clear and simple form that can be applied to the needs of specific patients with minimal time and effort. And veterinary students should be trained in the methods and benefits of epidemiology and an EBM approach and reminded of the weaknesses of informal and unstructured decision-making based primarily on experience and opinion.

The study authors conclude, quite reasonably:

Veterinarians make decisions in a complex environment, often quickly and rarely with an EBM approach. Obviously, this cannot mean that most practitioners make poorly

informed decisions…Two separate worlds seem to exist, academic research and the reality of practice, that need to join, probably by making the effort to include data from practice into research. Both worlds should also meet more in the field of education, where students should be trained in the complexity of contextualized decision making. More important, aside from those efforts to facilitate the development of evidence-based, accountable, and transparent veterinary medicine, there should be initiatives to scientifically demonstrate the benefits of an EBM approach for animals and owners, which would probably facilitate its adoption by veterinary practitioners.

Adequate information and EBM tools are needed to optimize the time spent in query and assessment of scientific information, and practitioners need to be trained in their use.

 

Posted in Science-Based Veterinary Medicine | 7 Comments

USDA Confronts Misleading Hype about Antioxidants in Foods

Posted on June 17, 2012 by skeptvet

I have commented a few times on the issue of antioxidant supplements. While the theory that some diseases are caused by, or at least involve in some way, oxidative damage is reasonable, and there are lots of in vitro studies showing both the negative effects of free radicals and the antioxidant effects of many chemicals found in foods, the clinical data that one can prevent or treat specific diseases with antioxidant supplements is virtually nonexistent. The hype about antioxidants far exceeds the evidence (c.f. this article also) of any real value, and some evidence has developed showing that they have significant potential risks, including increasing the likelihood of some diseases and interfering with some kinds of medical therapy. So while the potential uses of antioxidants deserve further study, the automatic assumption that they are a good idea is increasingly contradicted by the evidence.

So it makes sense that the US Department of Agriculture has withdrawn a public database it had maintained since 2010 showing one possible measure of the antioxidant capacity of certain foods. The Oxygen Radicals Absorbance Capacity (ORAC) consisted of a variety of in vitro chemical measures for the potential antioxidant effects of certain foods. While this might be useful information in planning research, it was not appropriate as support for health claims, and yet this is how the data was routinely being misused. The USDA notice makes the following important points:

[There is] mounting evidence that the values indicating antioxidant capacity have no relevance to the effects of specific bioactive compounds, including polyphenols on human health.

There is no evidence that the beneficial effects of polyphenol-rich foods can be attributed to the antioxidant properties of these foods.

The data for antioxidant capacity of foods generated by in vitro (test-tube) methods cannot be extrapolated to in vivo (human) effects and the clinical trials to test benefits of dietary antioxidants have produced mixed results.

We know now that antioxidant molecules in food have a wide range of functions, many of which are unrelated to the ability to absorb free radicals.

All of these points simply acknowledge that the evidence from epidemiological studies that consuming certain foods is associated with lower risk of certain diseases may have nothing at all to do with the antioxidant hypothesis of the antioxidant capacity of chemicals in these foods. In fact, the evidence is growing that whatever the health benefits may be of eating such foods, it probably has little to do with their antioxidant activity.

However, the most important reason for taking down the database was not simple scientific accuracy but the deliberate misuse of the information to support unproven health claims. As the USDA announcement put it,

ORAC values are routinely misused by food and dietary supplement manufacturing companies to promote their products and by consumers to guide their food and dietary supplement choices.

Because uncritical acceptance of the notion that antioxidants are good for you is widespread, despite limited supporting data and some data against this hypothesis, supplement manufacturers have been using the USDA ORAC data to add legitimacy to unfounded marketing claims about the health value of their products. Undoubtedly, of course, manufacturers of supplements with purported antioxidant activity will find other ways to promote this as having health benefits despite the lack of string evidence to back up such claims. But it is encouraging to see the government acknowledge that such marketing strategies are not consistent with good science and to make an effort not to accidentally support them.

 

 

 

 

Posted in Herbs and Supplements | Leave a comment

Latest Review Finds Fish Oils Don’t Help Dementia

Posted on June 13, 2012 by skeptvet

Fish oils are the current wonder supplement, good for all that ails you. I have actually taken them when the evidence appeared to support a benefit in prevention of cardiovascular disease, but the evidence is not looking as strong these days even for that indication, which has been the most strongly supported of the many suggested uses in humans. Other uses include prevention or treatment of dementia, arthritis, inflammatory diseases, and many others.

I have reviewed in detail suggestions that fish oils might have a benefit for arthritis in dogs, and it is weak but not definitive either way. Others have reviewed the use of fish oils in dogs with allergic skin disease, and there is reasonable evidence of some mild benefits for that condition. There have been suggestions that fish oils, as supplements or added to dog food, can affect the development of canine cognitive dysfunction, but there is no robust research evidence to support this.

A recent Cochrane review looking at fish oil supplementation and dementia in humans did not find evidence to support a beneficial effect despite a number of quite large clinical studies.

Emma Sydenham. Alan D Dangour. Wee-Shiong Lim. Omega 3 fatty acid for the prevention of cognitive decline and dementia.

Three randomized clinical trials involving over 4000 people were reviewed. Some subjects were supplemented and followed for as long as 2 ½ years. Despite this, no evidence of benefit was found. Few adverse events were seen either, apart from gastrointestinal upset. The conclusion of the review was:

Direct evidence on the effect of omega-3 PUFA on incident dementia is lacking. The available trials showed no benefit of omega-3 PUFA supplementation on cognitive function in cognitively healthy older people. Omega-3 PUFA supplementation is generally well tolerated with the most commonly reported side-effect being mild gastrointestinal problems.

Certainly not the last word, but yet another fairly strong piece of evidence suggesting that even one of the most intensively studied and widely used supplement has yet to definitively demonstrate the benefits claimed for it. And while data of similar strength is unlikely to be developed for dogs with cognitive dysfunction, the tentative conclusion based on extrapolating from the human research has to be that fish oils could have benefits in this condition, but it is at least as likely that they do not.

 

 

 

Posted in Herbs and Supplements | 7 Comments

Thank You Lewis Carrol

Posted on June 12, 2012 by skeptvet

Comments like the latest in the Double Helix Water thread always make me think of this:

“Alice laughed: “There’s no use trying,” she said; “one can’t believe impossible things.”

“I daresay you haven’t had much practice,” said the Queen. “When I was younger, I always did it for half an hour a day. Why, sometimes I’ve believed as many as six impossible things before breakfast.”

Alice in Wonderland.

Posted in Humor | 1 Comment

Resveratrol–Still Promising and Unproven, and Now With its Own Scandal

Posted on June 11, 2012 by skeptvet

Quite some time ago, I wrote about the substance resveratrol as an ingredient in a nutraceutical intended to treat canine cognitive dysfunction. Here was my conclusion at the time:

Resveratrol is a chemical extracted from grapes that has been touted as a general anti-aging panacea. There are numerous in vitro and lab animal studies that suggest the compound may act as an antioxidant and have a variety of effects promoting and inhibiting the expression of a number of genes. There is mixed evidence in lab animals that it may prolong life and inhibit, or in some cases promote, cancer. Human clinical trials for a number of possible uses are ongoing, but no data is available to suggest safety or efficacy for any particular use.

Likewise, there are apparently no veterinary clinical trials of resveratrol alone for cognitive and behavior dysfunction. As the newspaper article quoted above suggests, it is a promising but unproven compound which has been marketed well in advance of reliable evidence to its safety and efficacy. Resveratrol is an ingredient in Senilife, which has only weak supporting research evidence for clinical benefit in veterinary patients.

The latest reviews of the human literature suggest that the evidence hasn’t changed much; still promising but unproven.

Vang O, Ahmad N, Baile CA, Baur JA, Brown K, et al. (2011) What Is New for an Old Molecule? Systematic Review and Recommendations on the Use of Resveratrol. PLoS ONE 6(6): e19881. doi:10.1371/journal.pone.0019881

The overall conclusion is that the published evidence is not sufficiently strong to justify a recommendation for the administration of resveratrol to humans, beyond the dose which can be obtained from dietary sources. On the other hand, animal data are promising in prevention of various cancer types, coronary heart diseases and diabetes which strongly indicate the need for human clinical trials.

Quackwatch Summary

Epidemiologic studies can find associations between the consumption of foods or dietary supplements and various health outcomes. Animal experiments can demonstrate what can happen in the species tested. However, only human clinical trials can determine whether supplementation is useful for humans. Resveratrol has not been tested in clinical trials, and most clinical trials of other antioxidants have failed to demonstrate the benefits suggested by preliminary studies. Some substances—most notably beta-carotene—have even produced adverse effects. My advice is to ignore the hype surrounding resveratrol and eat a balanced diet that contains adequate amounts of fruits and vegetables.

There doesn’t appear to be any clinical trial literature on the subject in dogs or cats.

An interesting twist to this story involves one of the most visible researchers promoting resveratrol, Dipak Das from the University of Connecticut. In January, Dr. Das was charge by his university with multiple counts of fraud for falsifying and fabricating data. Since then, 12 of his published papers have been formally retracted. He has published 117 articles on the subject of resveratrol, many of which have been cited numerous times, so this could have some impact on the reliability of the evidence concerning resveratrol, though other researchers in the area contend Dr. Das’ work is not central to the field. In any case, it is a fine example of both the dangers of excessive and premature commitment to a hypothesis and promotion of products based on it as well as of the ultimately self-correcting nature of the scientific process.

Posted in Herbs and Supplements | 2 Comments

SuperVets: Entertainment, Education, or Propaganda?

Posted on June 10, 2012 by skeptvet

It is a well-known, indisputable, and nearly universally ignored fact that anecdotes in medicine are unreliable when trying to decide which therapies work and which don’t. The experiences of individual patients don’t even reliably tell us what worked or didn’t work in that specific case, and they certainly can’t be trusted to guide our treatment decisions for other patients. Health and disease are complicated, with numerous factors operating simultaneously to affect the outcome of any one patient, and there are a nearly infinite number of ways we can be fooled into thinking something is helpful which does nothing or even makes the problem worse.

The classic example is bloodletting, which was acclaimed as a rational and effective therapy by the greatest minds in medicine for thousands of years despite being not only ineffective but dangerous, sometimes even fatal. But there are many other such examples, both ancient and modern, of how telling stories about single patients leads us into false beliefs. The success of modern medicine, and the dramatic improvement in the length and quality of our lives in the last couple hundred years, is due to the shift from reliance on experience, history, and anecdote and towards trust in rigorous scientific methods for making decisions about medical therapies.

Unfortunately, anecdotes are not only unreliable, they are deeply compelling psychologically. We are storytelling creatures for whom creating and sharing narratives is a powerful way of building and maintaining our beliefs. It is in our nature to trust the stories we hear, especially when those stories agree with beliefs we already hold. So the rational evidence that stories are untrustworthy usually loses out to the emotional impact such tales have.

The only thing more misleading in medicine than an anecdote is a stylishly produced anecdote on television. Yet this is precisely the intended format for a proposed new television program aimed at promoting alternative veterinary therapies. Humbly named “SuperVets,” this program sounds like the perfect storm for swamping reason and science in a flood of emotional storytelling.

According to an interview for the VIN News Service, the idea for the show came from a television producer who is a believer in so-called holistic veterinary medicine. After meeting a couple of veterinarians who offer some unconventional therapies, the producer decided to create a television show that highlights “specialty veterinary medical services that many pet owners don’t realize are available.” Given that the teaser for the program talks about acupuncture, Chinese Medicine, and hyperbaric oxygen therapy, it seems likely that many of these therapies are going to be alternative approaches which have little scientific evidence to support them and so rely primarily on anecdotes for justification.

The format of the show is apparently to present heartwarming miraculous recoveries due to unconventional therapies, with no discussion of the scientific plausibility or research evidence concerning these treatments or any of the reasons why such anecdotes might not accurately represent reality. The teaser focuses on an adorable retriever, with an equally adorable and loving family. Supposedly condemned to death for some unspecified neurological disease by three different veterinarians, the dog is treated by one of the SuperVets with hyperbaric oxygen therapy, and the trailer ends by parading the apparently completely recovered patient before a live audience.

The producer describes this format as a “genre-defying show…staged before a live audience as well as in the field [that] uses real cases to educate viewers.” My understanding of the difference between education and propaganda is that the former includes a reasonably thorough and accurate presentation of information and the limits of our knowledge whereas the latter presents oversimplified narratives with only one possible interpretation. Apparently, the folks behind the show and I use the word “educate” differently.

Of course, there is nothing wrong with using anecdotes to illustrate an idea. It would be foolish to ignore the impact personal stories have on an audience. The trouble is when one uses anecdotes to prove something or to make a case for an idea that scientific evidence suggests is false. Since the show hasn’t been made yet, I can’t be certain that there won’t be thoughtful and informative information about the pros and cons of veterinary therapies, both conventional and alternative. But the teaser doesn’t give any indication this will be the case. And in the words of one of the SuperVets, “through modern veterinary medicine and emerging alternative therapies such as acupuncture and hyperbaric oxygen therapy, there are enough amazing recovery cases to present on the show for an indefinite period.”

I would certainly applaud an effort to show, in an enjoyable and compelling way, that veterinary medicine can be a sophisticated and successful enterprise. However, simply showing a series of supposed miraculous cures brought about by alternative medicine when conventional methods have failed or not been tried is purely propaganda, not education in any honest sense.

It isn’t that an entertaining and compelling show couldn’t be made about scientific medicine, complete with acknowledgement of its failures and limitations as well as its enormous success. Carl Sagan’s Cosmos is the paragon of moving, poetic depictions of legitimate science. And folks like Neil DeGrasse Tyson and Richard Dawkins are keeping alive the tradition of simultaneously accurate and beautiful depictions of science. Unfortunately, this project looks does not look to be in that vein. It appears instead to be a case of true believers in unconventional therapies cherry-picking and crafting supporting anecdotes to show a very skewed picture of alternative veterinary medicine. I guess we’ll know for sure if the project eventually makes it to television.

Posted in General | 3 Comments

N-Acetylcarnosine Eyedrops for Cataracts in Dogs and Cats (Can-C, Bright Eyes NAC, etc)

Posted on May 23, 2012 by skeptvet

A client recently asked for my opinion about the value of some over-the-counter eye drops purported to treat cataracts in dogs and cats. Not having read much about this product, I did a little research.

What Is It?
There are a number of eye drops marketed for prevention or treatment of cataracts in humans and pets. Most commonly, they contain a chemical called n-acetylcarnosine, which is made up of a couple amino acids and an acetyl group. In vitro research suggests this chemical has anti-oxidant effects, so it has been hypothesized to prevent or reduce the gradual opacification of the lens of the eye through this mechansism. As I have pointed out before, the role of oxidative damage in disease, and the value of anti-oxidant therapies, is a developing area of research. Many of the exuberant and enthusiastic hopes in this area have proven false, so while it is an area deserving further investigation, claiming something is an anti-oxidant is not automatic validation of its safety or benefits (e.g. 1, 2, 3).

Does It Work?
There have been a number of studies of n-acetylcarnosine, both in vitro studies and clinical trials in humans. Interestingly, almost all of these appear to have been published by the same researcher and his team, Dr. Mark Babizhayev. A clinical trial was published in 2001 (and it appears the same data was published again in a different journal in 2002, which if true is quite a significant science no-no). The trial was randomized and controlled in a small number of patients, and it appeared to show significant changes in a number of objective measures of cataract severity.

I am not familiar with the specific techniques used to measure the disease or response to treatment, so I will presume they are standard and appropriate measures for this kind of study. One thing that is not clear from the published report is whether the individuals making these measurements were blinded to the treatment status. This obviously has a significant bearing on the reliability of the results, especially when they stem from only one researcher, as such debacles as the Benveniste affair show.

A number of subsequent papers have been published by Dr Babizhayev and his team, mostly in vitro or lab studies investigating properties of n-acetylcarnosine, not clinical trials. Dr. Babizhayev has also become the leader of a commercial firm marketing n-acetylcarnosine for cataract treatment, and many other uses (including skin care, wound care, respiratory disease, and neurologic disease).

This commercial effort, and the spreading of claims for n-acetylcarnosine to a wide range of apparently unrelated applications, does raise some questions about the reliability of Dr. Babizhayev as the sole source of scientific validation for this compound. Overall, the status of the evidence for use of n-acetycarnosine for cataracts in humans is best summarized by the Royal College of Opthalmology:

 

The evidence for the effectiveness of N-acetyl carnosine eye drops is based on experience on a small number of cases carried out by a Russian researcher team. To date, the research has not been corroborated and the results replicated by others. The long-term effect is unknown.

Unfortunately, the evidence to date does not support the ‘promising potential’ of this drug in cataract reversal. More robust data from well conducted clinical trials on adequate sample sizes will be required to support these claims of efficacy.

Furthermore, we do not feel the evidence base for the safety is in any way sufficient

Unusually, there is actually some clinical trial evidence in veterinary species as well. An uncontrolled, unblended pilot trial has been published on an n-acetylcarnosine product (not the one Dr. Babizhayev sells) in dogs with cataracts.

David L Williams, Patricia Munday. The effect of a topical antioxidant formulation including N-acetyl carnosine on canine cataract: a preliminary study. Vet Ophthalmol. 2006 Sep-Oct;9(5):311-6. The results showed marginal improvement in all groups, though it was only significant in patients with 2 out of 5 types of cataract treated. However, subjectively owners reported improvement in 80% of the subjects.

Dr. Williams  has apparently performed a blinded, placebo-controlled follow-up trial on this product which did not show any benefits (in fact improvements were greater in the placebo group than in the treatment group), showing once again the importance of proper controls for bias, confounding, and other sources of error in clinical trials. Unfortunately, it appears unlikely this trial will be published for reasons which are not completely clear, though one implied issue is that journals are often reluctant to accept papers that show negative results, which are less exciting for readers than positive studies. All of this is, of course, through word-of-mouth among veterinarians, so I cannot confirm it is true.  

Is It Safe?
I have not found any reports of adverse effects from ophthalmic application of N-acetylcarnosine itself, and given its chemical makeup it seems unlikely to be hazardous. As usual, products containing this agent are not regulated as licensed medicines are, and there is no way to ensure label accuracy, proper manufacturing quality standards, or the safety of other ingredients that may be included with the N-acetylcarnosine. 

Bottom Line
The theoretical arguments for why this drug might be useful I the treatment of canine cataracts are plausible but largely unproven. There is limited clinical trial evidence in humans suggesting a benefit, but this has not been replicated and is at high risk of bias. The limited clinical trial evidence available in dogs does not suggest a benefit. There are minimal safety concerns with products containing N-acetylcarnosine.

Posted in General | 172 Comments