Happy 10th Blogiversary to Me!

Hard to believe, but my first post, What is Open-Mindendess?, appeared June 4, 2009. Lots of things have changed in the ten years since I began this blog. My subjects and the tone of my writing are often different from the early days. And I have been fortunate to have the opportunity to share my enthusiasm for evidence-based medicine and my skepticism in a wide variety of other venues, from veterinary conferences and journal articles to media interviews and my monthly column in Veterinary Practice News. It’s impossible to know what the impact of this work is, but despite the steady trickle of hate mail it generates, I get a lot of support from folks in the veterinary field and also animal owners who find the ideas and information I share useful. I shared some of this positive feedback on my 5th Blogiversary post, and I will continue the tradition with some examples below.

I also want to celebrate the occasion with an announcement. As a further contribution to the cause of rational, evidence-based veterinary medicine and the health of our animal companions, I have spent a lot of time over the last few years working on a special project, and I happy to say that this work will finally come to fruition later this year in the form of a book for pet owners and veterinary professionals.

I can’t provide a lot more detail at this point, but my hope is that this will become a useful reference and an introduction to science-based veterinary medicine in the way that some of my favorite books, such as Don’t Believe Everything You Think and Trick or Treatment, have been for science-based human medicine.

Finally, thank you all for reading and for sharing the ideas information I pass along here. If we can help just a few people and their animals make sound, science-based decisions about healthcare for pets, we have done something worthwhile!


My dogs and cats appreciate the work you do. Alt med, and woo hucksters in general, don’t typically have a great moral compass. As skeptics, if we could shut off the ethical side of our brains, we could make loads of money.

@SkeptVetyou are fantastic, and any ridiculous insinuation that you have anything to do with the mental health crisis in the vet med world is entirely ludicrous. Thank you for all that hard work that you do! Please – keep it up!

Thank you for your truth and insight on various subjects. I have worked in the veterinarian field for over 20 years, and live in the same city as Rodney Habib. When I would question a few of his claims, he would block or ban me. As I was being respectful and professional in my questioning. I can only surmise he didn’t have evidence to back up his claims. We have seen many sick animals on the type of nutrition he preaches. He is a social media celebrity that is very slick with the smoke and mirror show when it comes to fear mongering pet owners against conventional and science based medicine. Too bad so many people listen to him, as he does give out much misinformation.

[SkeptVet] is one of the most knowledgeable, capable, thoughtful, insightful, thorough, caring, intelligent vet/person that I’ve had the pleasure of knowing and working with ever.

They believe what they want to believe no matter the evidence to the contrary. Thank-you so much for this article skeptvet…This saved my partner from wasting money & getting hopes up for nothing. … It upsets me to discover so many trying to profit off of others… creating false hopes from folks who’ll do just about anything to help their pet.

Thank you so much!…I really appreciate you taking the time to address my concerns and provide me with reliable –evidence based, and hallelujah for that!…I also appreciate you taking the time and effort to provide factual info in a world where “belief” grows ever more important than evidence….and being willing to take the attacks that arise because of your efforts.

Great response doctor
So proud of you as a fellow veterinarian

Thank you so much for this article and the associated comments. 

As a fellow veterinarian I applaud you for publishing true science and facts in the face of a continued stream of ignorance and hatred. Ours is an exhausting profession involving (in my case at least) ten years of university and two professional degrees. How anyone can insinuate that we are uneducated is beyond me. Carry on with the great work!

So pleased to discover this. Very interesting…I am so grateful for the time you take to write your opinions. Thanks.

Thank you SkeptVet for all the time and energy it must require to compose your thoughtful and well written blogs. I am trained as a pharmacist however I now work with horses, mostly training. I often feel very alone in my skepticism as horse people in general seem to be very susceptible to all kinds of blarney. I am also dismayed to find that a lot of folks have only a vague idea of how bodies function much less the realities of chemistry and physics. Your blogs have touched on things I come across all the time in the horse world and I often feel like the Lone Ranger in my skepticism or outright challenge of certain modalities that are accepted with no question. I try to be circumspect because alienating people does not advance my cause. But maybe I throw out a comment or two that might spark some investigation (e.g. most folks have no idea what homeopathy is, they think it is herbs or home remedies). Most of the time this goes nowhere but on rare occasions I can change someone’s thinking. So thanks for letting me know I’m not alone.

Absolutely! Positively! I couldn’t agree more. Thank you, skeptvet, for writing this piece, and thank you, Veterinary Practice News, for also publishing it!

After reading the kind of response you get from those who disagree with the importance of skepticism in medicine, I appreciate the work you do even more so. I am about to head into a small animal internship, and the value of science based medicine when available can’t be any more important. I take this into account with my own health and medicine too. Thank you for your inspiration!

Sorry you are the target of so much rage and outrage. I must admit, it’s puzzling to me, too, why so many people who don’t agree with you get so upset and vicious about it.

As a counterpoint, let me say that I GREATLY appreciate all the research and time you put into creating this blog–it’s a wonderful and unique resource for those of us who value evidence-based medicine. I never realized how little it’s actually being practiced out there til I started reading your articles. I really rely on your analyses and only wish you could cover even more topics!

Wow. I am not skimmed a few, and found them pretty strange and not great reading. I admire you for your balanced viewpoint and for remaining courteous – not something most of your detractors manage, I see. Thank you for writing and thinking.

As I have said before I really appreciate the effort you put into this blog, when you could no doubt be doing far more entertaining things or even just sleeping. I also appreciate that you manage to maintain a polite tone, while I love me some Respectful Insolence the field of sceptical scientific bloggers is small enough that we still need all of the straight analytical posters we can get. So once again THANK YOU!!!!!!

Wow, that’s some heavy stuff. I applaud you for expressing enough clear opinion to piss people off. 

Thank you for your quick and helpful response!

Hello there. I *really* admire and enjoy your blog posts. I have forwarded a link to this latest one to several more junior colleagues who are very interested in this topic…I find your work on this blog outstandingly good and very enjoyable.

I really appreciate this blog.

Excellent commentary, as usual.

I appreciate your blog and I am so glad that I found it several years ago. You provide a great service, especially for pet owners such as myself. The articles you have published have helped me have informed opinions about different alternative treatments. Plus, your discussions about EBM approaches in conventional medical care have helped me understand how to better discuss and interact with our vets when we seek care for our poodles.

I love this blog and check it often…Thanks for all your writing, time and assistance.

I love this blog. You have no idea how much. I’m a retired pharmacist and I like my medicine evidence based and my science peer reviewed. You are a rare voice in the blogosphere these days but a badly needed one. I am constantly getting in heated discussions over woo. I recently saw someone suggest a person nebulize their sick puppy with colloidal silver. I nearly swallowed my tongue but I could not keep quiet in the face of such insane ideas. I often think we are totally losing the battle for common sense and good judgement. I would be even more depressed if not for your blog.

I just came across your blog as my husband asked me to look at an herbal product being marketed for Cushing’s. Our 14 year old mixed breed dog has this. She is on Vetoryl. I am a retired psychologist who knows the value of relying on good scientific research. I just wanted to tell you that I appreciate your good advice and will be following your blog. I may be asking for some of your advice in the future.

Someone recommended ozone therapy for my dog who is having repeating diarrhea episodes…It sounded like homeopathic/holistic nonsense to me from the description I read so I thought “where can I get some reliable info on this?” Of course I came to you first. Thank you for providing facts and reliable information on these types of subjects so those of us who shun all the hocus pocus inflicted on our animals in the name of healing can make informed decisions and feel better about telling well-meaning people “no, thanks!”

I appreciate your website and insightful comments, and I agree that a few individual cases do not amount to proof…Thank you!

Thank you so much for the information provided on your website. I have been working for an Internal Medicine Practice for 12 years under 3 Dip. ACVIM doctors. On currently practicing for 47 years. As time goes by more and more of our clients are being stooped into believing non-science based information they read online. Most recently, Glacier Peak Holistic Pet Life Scan. I have provided my client with your review of their rubbish. Thanks again!!!

We need more vets like you fighting for veterinary medicine to be based on the same requirement for evidence that human medicine is.

I just want to say I am really enjoying the site and I am learning lots which is always good

Thank you. Your reply has done more good than you may realize. ?? Compassion and science – a powerful medicine.

Your website is invaluable for accurate information.   Thank-you!  

Excellent article, thank you for your efforts.

If I had an animal, you would be my vet.

Just found this in a Google search on standard process. I love the thoughtful analysis.

I really, really wish I’d found this post–or something similar, lol–5 years ago. Thanks.

Thank you so much! There are so many anecdotal stories about these products (and everything dog related) online, which as you point out, does not constitute evidence. I sincerely appreciate such a considered post. You are doing great work, it’s often difficult to separate marketing from real science when dealing with a pup with behavioural issues and I’m so glad to see someone working to address this.

Since I found this blog a while ago I’ve been a fan. The main problem I have is that a lot of veterinarians will advertise “acupuncture”, “traditional Chinese medicine” or “holistic” (which generally has acquired a different meaning than just “considering all aspects”). It seems to be not easy to actually find a veterinarian who tells you that they are doing science based medicine. It leaves me as a pet owner to try to check up on the vet (refused to buy glucosamin supplements from 3 different vets so far) and trying to figure out what aspects of their medical practice I can trust and which I can’t. I tend to come here to check.

Dear Skeptvet
I too was happy to stumble on your blog via the NPR article , while browsing “News” on my phone. Having spent 13 years in scientific research before becoming a vet, I was originally shocked by the idea that medicine was NOT entirely evidence based. I just assumed it would be. But after ten years in practice I am getting worn down by the lack of rigorous data
And scientific information, pressure of colleagues, pressure of pet owners to practice unproven methods left and right. It is great to have your reasoned voice out there. I hope more pet owners will come across your blog.

I came to your blog after a friend posted your interview. I have now book marked your blog! Keep advocating for science based medicine – my dogs thank you for it.!

I just found your blog through the NPR interview and have been impressed while perusing it. Thanks for the enormous amount of time, effort, etc. you’ve devoted to this fantastic resource. As a pet owner (2 cats) with longtime professional expertise in research synthesis — mainly meta-analysis — and personal interest in scientific skepticism, I’m heartened to see this sort of critical thinking emphasized for the well-being of creatures who depend heavily on their vets and owners to make responsible healthcare choices.

I can say that it would have been extremely helpful to have had the benefit of this blog at the time we were weighing our options. Thank you for this site, which does an excellent job of providing fact based information to assist in making critical choices about the care and well being of cherished members of our family.

I am new here. I appreciate what you do. Found out about you on NPR. Thank you for taking the time to do this.

P.s. love your site, as usual. Many hours slip away from me some days perusing and reperusing your very entertaining and thoughtful analyses :b

As a professional, you are always one of my first choices to take care of my pets or someone that I refer others to take their pets to. Your open mindedness, willingness to look at the whole picture and willingness to listen to the client about their concerns makes you very competent in my eyes. Screw this tool who doesn’t even know you.

And to @Skeptvet, I just came across your site today in trying to do research on this product as it was prescribed for one of my patients. I am impressed with what I have read, and if this is any indication of the rest of your site, bravo to you for such a thoughtful, helpful and fact-based approach to the problems many owners confront. Keep up the good work.

I am so glad I found this site. Keep it up! Many more clients asking about ‘Veterinary naturopaths’ these days.– a concerned DVM student

Thanks for your clear explanations, skeptvet.

On another note, thanks for your blog, @skeptvet. I consult it frequently to help me keep my eye on the ball when it comes to the care of my digestively challenged, highly allergic white boxer/staffie angel. 

Thank you for this article, I am very glad I stumbled across you.

As another evidence-inspired practitioner, I am grateful for the time and effort Skeptvet puts forth in this continuing discussion.

This is EXACTLY what I needed as we try to understand what’s happening with her kidneys, and as we look to exhaust all of the options that are both within our financial reach and that are most likely to have a positive impact on her health. Thank you.

I want to thank you for doing this.

Not everyone can contact a friend and have her go to a friend who is a knowledgeable veterinary researcher. I am glad your site exists. There’s so much trash out there, it’s good to have a voice of reason.

I love this skepticism! People need to see a balance of ideas and decide for themselves what resonates with them.

I just wanted to check, is it okay if I quote you from time to time? I would always provide the link to the article and your website.
I have been doing this, but wanted to know if it was okay?

Your site has been very helpful . Thanks For sharing information.

Thank you so much for taking the time to provide clear thought and information on these topics, Skeptvet. I just learned of your site from a friend’s post and I can’t stop reading. I appreciate all the work you have done to lay out the evidence and arguments, with explanations of how the scientific process works, and how to evaluate information. We need science more than ever!

Thanks for your blog! I’m a pet owner, and I’ve noticed that a number of local vets are into various practices that I’m sceptical of. (I’m from Canada; that’s how we spell sceptic.) Despite my doubts, I just tried hemp oil for my dog’s chronic rhinitis; no effect. Back to proven Western meds.
It was great to see you quoting the Cochrane folks! Carry on!

I want to thank you also; your website provides good information and helps me avoid quackery. 

Thank you for doing this. I hope you have something that works to ‘clean’ your brain after going through so much dross.

I, too, thank you. A few months ago, before finding your website, I would have watched the series and believed it all: anti-vaccine, anti-preventative, raw food, holistic. Now i’m using Dog Food Logic to try to figure out what kibble to feed our new dog. Where do I send the Scotch??

Hopefully people are drawn to your blog since it’s extremely well researched and presented. Thanks again for everything you do!

Hi there. I reguarly seek refuge in your blog when I’m bombarded by client questions on homeopathy, natural remedies, and, the product do jour, CDB oil.

I just discovered your blog tonight. Thanks so much for this! Wow — what a tremendous amount of work you put in to helping people make informed decisions in a confusing world of real and bogus (or at least, unbacked) treatments. Much appreciated!

Thank you for your refreshing blog. I am constantly frustrated by  clients who insist various non-sense treatments work, as opposed to my science based treatments. Of course, their perception is that I am just out to make money (aren’t all veterinarians? because we went into this field to make money??)

Thank you for helping me verbalize these ideas to my clients.

I am a physician and much appreciate your fine web site. Keep up the great work!!

Skeptvet, Firstly I’d like to thank you for your efforts in advocating for science based veterinary medicine. I’ve been a big fan of Dr Steven Novella and his efforts in human medicine and one of the few people I trust for good information. Your blog has become my go to source for advice regarding my dogs.

Thank you for getting back to me, and for spending so much time and effort helping to promote good, evidence-based medicine and stamping out quackery.

I love your blog by the way.  Its nice to read pet/animal information that is presented in a factual and scientific way instead of all the bogus stuff on the internet that essentially tries to tell you that you are killing your dog/cat if you are/aren’t doing “xyz”.  No research, no trials, no really any information to back it up with, just people spouting what they think.

Keep up the good work!

Thank you for this site! I’m a bit of a helicopter cat mom and have read so many articles debating certain ingredients in cat foods—namely carrageenan and menadine sodium bisulfate complex. I recently added weruva to my kitty’s rotational diet and kicked myself for feeding him something MSD in it after seeing it on the label until I read this!! Thanks so much for putting my mind at ease.

Your extremely articulate writing and your views are a breath of fresh air amidst what I sometimes feel is pure insanity. You are not alone, although even within the vet community it sometimes feels that way.

I just want to say “thank you.” Finding your blog fills me with relief – that I have someone to go to who uses critical thinking skills to produce relevant, science-based information about veterinary medicine…Screw those critics. Rock on.

Just want to say thank you for producing such amazingly educating contents with scientific rigor and empirical prudence. In this crazy milieu teeming with paranoiac pet parents and cultish advocates (with all due respect to those who aren’t), it is hard to find a public platform like yours with a voice so scientifically careful yet reassuringly informative. Keep up the good work!

I’m a PHD chemist, and I get a lot of questions from my friends about woowoo stuff. You blog is a REAL breath of fresh air. You focus on the science, you do not condemn (despite that fact that I would want to slap some commenters silly). Keep doing what you are doing. It really is appreciated.

Posted in Uncategorized | 9 Comments

Should I Worry About Bacteria in My Pet’s Urine? Well, It Depends….

Veterinarians and pet owners are highly motivated to find discrete, fixable problems when pets are unwell. Owners want the reassurance and sense of control that comes with knowing what the problem is and taking action. Vets want to help our patients, and we want to satisfy our clients, who often expect us to offer some clear preventative or therapeutic intervention, which can justify their time and expense coming to see us and reassure them about their pets’ condition. Finally, our medical training often emphasizes diagnosis and treatment as the core responsibility for a doctor, and the importance of knowing when not to take action is frequently underemphasized.1,2

Such inherent bias towards finding and treating problems creates discomfort and resistance when scientific evidence suggests we should avoid some tests or treatments. Though there is widespread awareness of the risks of overdiagnosis and overtreatment in human medicine, these are relatively new and controversial concepts in the veterinary field.3,4My own efforts in this column and elsewhere, to suggest that we might sometimes do better not to run a test (e.g. pre-anesthetic bloodwork)5or prescribe a treatment (e.g. lysine)6have generated the kind of pushback that often greets such suggestions. 

Nevertheless, we have a responsibility to heed the evidence and recognize when inaction may serve our patients better than intervention. One example of this that is beginning to gain some attention in veterinary medicine is subclinical or asymptomatic bacteriuria (AB).7This is most simply defined as the presence of bacteria in urine without clinical signs compatible with a urinary tract infection (UTI).8–10The definition of AB may also include a threshold quantity of bacteria grown on culture and repeated positive urine cultures, to distinguish AB from transient bacteriuria and contamination of the urine sample.11,12

In humans, the presence of bacteria without symptoms of UTI is quite common, though the prevalence varies with sex, age, and many other factors. Less than 5% of healthy, pre-menopausal women have AB, whereas 100% of people with chronic indwelling urinary catheters will have bacteriuria even when no symptoms of UTI are present. Prevalence is higher in the elderly, diabetics, and people with some other causes of immunocompromise.8,12

Despite this high prevalence, there is substantial research showing most people with AB do not benefit from antibiotic therapy.8,12–14Even in diabetics, the elderly, and other individuals with potentially compromised immune function, AB does not seem to increase the risk of negative outcomes, and treatment with antibiotics provides no benefit and may even cause harm.12,14Antibiotic treatment for humans with AB appears to be beneficial for only a very limited set of circumstances, such as in pregnancy and prior to transurethral resection surgery.11

Clinical practice guidelines for physicians recommend against screening and treatment for AB in most patient populations.11,12Despite this, many physicians will still prescribe antibiotics when they diagnose AB, particularly if pyuria or other findings are present that they believe indicate UTI even when the evidence does not support this practice.  Education programs have been employed to reduce this inappropriate antibiotic use because it can increase patient morbidity and antibiotic resistance.8

It is less clear how common AB in dogs and cats. Studies have found highly variable prevalence, from 28% to less than 1% of samples in cats15–20and from 25% to 0% of samples in dogs.9,10,21The occurrence of AB appears to vary with many factors, including species, sex, age, body condition score, and presence of potentially predisposing diseases.7,10,15,17–19,21,22Morbidly obese dogs, for example, appear more likely to have AB than dogs with less extreme body conditions scores.21Females are often reported to have AB more frequently than males.17,23

Interestingly, some studies have failed to find any association between potentially immunosuppressive drug treatment and AB even though such medications have been reported to increase the risk of urinary tract infections.20,24–26An increased risk in the presence of chronic kidney disease (CKD) has been seen in some reports but not others.9,17

Unfortunately, most of the studies in veterinary patients have evaluated small numbers of patients, and they have varied methods and numerous limitations which it challenging to compare studies or have much confidence in the results. Sufficient detail is lacking to clearly identify associations between specific patient characteristics and the prevalence and risk of AB. This makes it more difficult to challenge the reflexive urge many of us have to treat bacteriuria whenever we see it despite the strong evidence in humans that this may not always be best for the patient.

The limited veterinary evidence available does suggest that AB is not likely to be a predictor or cause of subsequent disease.10,19However, this conclusion must be viewed as tentative given the strength of the evidence. The most recent guideline from The International Society for Companion Animal Infectious Diseases offers the following recommendation:27

“Treatment may not be necessary in animals that have no clinical signs of UTI and no evidence of UTI based on examination of urine sediment. 

In some circumstances, treatment may be considered if there is concern that there is a particularly high risk of ascending or systemic infection (e.g., immunocompromised patients, patients with underlying renal disease) or that the bladder may be a focus of extra-urinary infection.”

This is necessarily a far more tentative recommendation than guidelines for physicians due to the paucity of high-quality research evidence. Nevertheless, it reflects a growing awareness that treatment of AB is likely to be unnecessary in at least some veterinary patients and, as in humans, it may lead to increased antibiotic resistance and poorer clinical outcomes. 

There is also research in humans showing that colonization of the urinary tract with non-virulent bacteria can protect against more virulent, and more antibiotic-resistant varieties. Such bacteria have been used clinically to reduce the risk of symptomatic UTI and more serious sequelae, such as pyelonephritis.12,28AB was once considered a probable cause of pyelonephritis, but it is now recognized as benign or even a potentially protective condition.12

Research has been conducted to evaluate this potential prophylactic use of non-pathogenic organisms in dogs.29–31In one study, instillation of  an E. colistrain obtained from an individual with AB into dogs appeared to have no significant risks, and it may have been effective in treating and preventing some naturally occurring UTIs. The study was small and uncontrolled, so further research will be needed to confirm the safety and efficacy of this practice.

Bottom Line
In the absence of conclusive evidence for veterinary species, individual clinicians must decide how to manage apparent cases of bacteriuria. While extrapolation from human medicine is not always reliable, it is a common starting point for making clinical decisions in veterinary patients. In cases when bacteriuria is identified and when there are no apparent clinical signs of UTI and no special circumstances (such as advanced age, immunosuppressive disease or medical treatment, etc.), it is reasonable for veterinarians to choose not to provide antibiotic therapy. We must, of course, explain to clients the reasoning for this choice, including the goal of avoiding harm from unnecessary treatment, in the form of medication side-effects and potentially more dangerous and drug-resistant UTIs. 

When treating AB or uncomplicated UTI, we should also bear in mind that 3-5 days of treatment is the standard in human medicine.32–34Though again the evidence is not yet conclusive in veterinary patients,35it is likely that longer treatment only increases complications and reduces compliance without improving outcomes for our patients.


1.        Vandeweerd J-M, Vandeweerd S, Gustin C, et al. Understanding Veterinary Practitioners’ Decision-Making Process: Implications for Veterinary Medical Education. J Vet Med Educ. 2012;39:142-151. doi:10.3138/jvme.0911.098R1

2.        McKenzie BA. Veterinary clinical decision-making: Cognitive biases, external constraints, and strategies for improvement. J Am Vet Med Assoc. 2014;244(3). doi:10.2460/javma.244.3.271

3.        McKenzie BA. Overdiagnosis.J Am Vet Med Assoc. 2016;249(8). doi:10.2460/javma.249.8.884

4.        Welch H, Schwartz L, Woloshin S. Overdiagnosed: Making People Sick in Pursuit of Health. Boston, MA: Beacon Press; 2011.

5.        McKenzie B. Why do we run diagnostic tests? Vet Pract News. February 2018:38.

6.        McKenzie B. Lysine: A therapeutic zombie? Vet Pract News. May 2018:26-28.

7.        Senior DF. Subclinical Bacteriuria. Clin Br. November 2018:61-64.

8.        Flokas ME, Andreatos N, Alevizakos M, Kalbasi A, Onur P, Mylonakis E. Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis. Open Forum Infect Dis. 2017;4(4):ofx207. doi:10.1093/ofid/ofx207

9.        Foster JD, Krishnan H, Cole S. Characterization of subclinical bacteriuria, bacterial cystitis, and pyelonephritis in dogs with chronic kidney disease. J Am Vet Med Assoc. 2018;252(10):1257-1262. doi:10.2460/javma.252.10.1257

10.      Wan SY, Hartmann FA, Jooss MK, Viviano KR. Prevalence and clinical outcome of subclinical bacteriuria in female dogs. J Am Vet Med Assoc. 2014;245(1):106-112. doi:10.2460/javma.245.1.106

11.      Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults. Clin Infect Dis. 2005;40(5):643-654. doi:10.1086/427507

12.      Nicolle LE. The Paradigm Shift to Non-Treatment of Asymptomatic Bacteriuria. Pathog (Basel, Switzerland). 2016;5(2). doi:10.3390/pathogens5020038

13.      Bigotte Vieira M, Alves M, Costa J, Vaz-Carneiro A. Análise da Revisão Cochrane: Antibióticos Destinados ao Tratamento da Bacteriúria Assintomática. Cochrane Database Syst Rev. 2015;4:CD009534. Acta Med Port. 2018;31(2):76. doi:10.20344/amp.10077

14.      Köves B, Cai T, Veeratterapillay R, et al. Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel. Eur Urol. 2017;72(6):865-868. doi:10.1016/j.eururo.2017.07.014

15.      Litster A, Moss S, Platell J, Trott DJ. Occult bacterial lower urinary tract infections in cats—Urinalysis and culture findings. Vet Microbiol. 2009;136(1-2):130-134. doi:10.1016/j.vetmic.2008.10.019

16.      Teichmann-Knorrn S, Reese S, Wolf G, Hartmann K, Dorsch R. Prevalence of feline urinary tract pathogens and antimicrobial resistance over five years. Vet Rec. 2018;183(1):21-21. doi:10.1136/vr.104440

17.      Puchot ML, Cook AK, Pohlit C. Subclinical bacteriuria in cats: prevalence, findings on contemporaneous urinalyses and clinical risk factors. J Feline Med Surg. 2017;19(12):1238-1244. doi:10.1177/1098612X16688806

18.      Eggertsdóttir A V, Sævik BK, Halvorsen I, Sørum H. Occurrence of Occult Bacteriuria in Healthy Cats. J Feline Med Surg. 2011;13(10):800-803. doi:10.1016/j.jfms.2011.07.004

19.      White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C. Subclinical Bacteriuria in Older Cats and its Association with Survival. J Vet Intern Med. 2016;30(6):1824-1829. doi:10.1111/jvim.14598

20.      Lockwood SL, Schick AE, Lewis TP, Newton H. Investigation of subclinical bacteriuria in cats with dermatological disease receiving long-term glucocorticoids and/or ciclosporin. Vet Dermatol. 2018;29(1):25-e12. doi:10.1111/vde.12480

21.      Wynn SG, Witzel AL, Bartges JW, Moyers TS, Kirk CA. Prevalence of asymptomatic urinary tract infections in morbidly obese dogs. PeerJ. 2016;4:e1711. doi:10.7717/peerj.1711

22.      Koutinas AF, Heliadis N, Saridomichelakis MN, Leontides L, Terpsidis K, Christodoulou C. Asymptomatic bacteriuria in puppies with canine parvovirus infection: a cohort study. Vet Microbiol. 1998;63(2-4):109-116. http://www.ncbi.nlm.nih.gov/pubmed/9850991. Accessed January 7, 2019.

23.      White JD, Cave NJ, Grinberg A, Thomas DG, Heuer C. Subclinical Bacteriuria in Older Cats and its Association with Survival. J Vet Intern Med. 2016;30(6):1824-1829. doi:10.1111/jvim.14598

24.      Simpson AC, Schissler JR, Rosychuk RAW, Moore AR. The frequency of urinary tract infection and subclinical bacteriuria in dogs with allergic dermatitis treated with oclacitinib: a prospective study. Vet Dermatol. 2017;28(5):485-e113. doi:10.1111/vde.12450

25.      Torres SMF, Diaz SF, Nogueira SA, et al. Frequency of urinary tract infection among dogs with pruritic disorders receiving long-term glucocorticoid treatment. J Am Vet Med Assoc. 2005;227(2):239-243. http://www.ncbi.nlm.nih.gov/pubmed/16047659. Accessed January 20, 2019.

26.      Ihrke PJ, Norton AL, Ling G V, Stannard AA. Urinary tract infection associated with long-term corticosteroid administration in dogs with chronic skin diseases. J Am Vet Med Assoc. 1985;186(1):43-46. http://www.ncbi.nlm.nih.gov/pubmed/3965423. Accessed January 20, 2019.

27.      Weese JS, Blondeau JM, Boothe D, et al. Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases. Vet Med Int. 2011;2011:263768. doi:10.4061/2011/263768

28.      Darouiche RO, Hull RA. Bacterial interference for prevention of urinary tract infection: an overview. J Spinal Cord Med. 2000;23(2):136-141. http://www.ncbi.nlm.nih.gov/pubmed/10914355. Accessed January 20, 2019.

29.      Thompson MF, Schembri MA, Mills PC, Trott DJ. A modified three-dose protocol for colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972. Vet Microbiol. 2012;158(3-4):446-450. doi:10.1016/j.vetmic.2012.03.012

30.      Thompson MF, Totsika M, Schembri MA, Mills PC, Seton EJ, Trott DJ. Experimental colonization of the canine urinary tract with the asymptomatic bacteriuria Escherichia coli strain 83972. Vet Microbiol. 2011;147(1-2):205-208. doi:10.1016/j.vetmic.2010.06.007

31.      Segev G, Sykes JE, Klumpp DJ, et al. Evaluation of the Live Biotherapeutic Product, Asymptomatic Bacteriuria Escherichia coli2-12, in Healthy Dogs and Dogs with Clinical Recurrent UTI. J Vet Intern Med. 2018;32(1):267-273. doi:10.1111/jvim.14851

32.      Gupta K, Hooton TM, Naber KG, et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-e120. doi:10.1093/cid/ciq257

33.      Kang C-I, Kim J, Park DW, et al. Clinical Practice Guidelines for the Antibiotic Treatment of Community-Acquired Urinary Tract Infections. Infect Chemother. 2018;50(1):67. doi:10.3947/ic.2018.50.1.67

34.      American Academy of Family Physicians. R, Williams M. American Family Physician.Vol 84. American Academy of Family Physicians; 1970. https://www.aafp.org/afp/2011/1001/p771.html. Accessed January 28, 2019.

35.      Jessen LR, Sørensen TM, Bjornvad CR, Nielsen SS, Guardabassi L. Effect of antibiotic treatment in canine and feline urinary tract infections: A systematic review. Vet J. 2015;203(3):270-277. doi:10.1016/j.tvjl.2014.12.004

Posted in Uncategorized | 3 Comments

What are Screening Tests, and Should You Use them?

What is Screening?
Screening is the use of diagnostic tests in apparently healthy individuals with no clinical symptoms.1-2The purpose is to detect asymptomatic disease with the presumption that this allows earlier, more effective intervention and will reduce suffering and delay or prevent death. 

Screening is widespread in human medicine, though it is increasingly a subject of controversy and debate.3Large-scale programs in human medicine to promote testing for specific diseases have been widely used, such as prostate-specific antigen (PSA) testing for prostate cancer and mammography for detection of asymptomatic breast cancer. These are examples of screening programs which are now being questioned and scaled back in light of better evidence concerning their risks and benefits.4-5

However, any diagnostic test employed in an individual with no clinical symptoms of illness is a screening test. In veterinary medicine, there are few large-scale, coordinated screening programs, but routine well-pet exams are a common screening practice. There are also calls for more extensive and intensive screening efforts, such as the recent guideline from the American Animal Hospital Association (AAHA) and the large diagnostic laboratory IDEXX promoting routine lab testing for nearly all pets.6

How Does Screening Benefit Patients?
Most veterinarians understand the potential benefits of screening. Individual patients will benefit if a disease is identified which can be treated more effectively when asymptomatic than at a later stage. Some diseases can be delayed or even cured if treated at an early stage which cannot be so effectively managed if not detected until there are clinical symptoms. Identifying IRIS Stage 2 Chronic Kidney Disease and instituting dietary therapy is an example of effective screening and intervention.7-8This is what most of us assume all screening accomplishes.

True negative results might be considered beneficial as well in that they provide reassurance and, depending on the tests involved, potentially a baseline value that can be used for diagnostic purposes in the future, even though they don’t directly impact morbidity or mortality.

When Is Screening Not Beneficial to Patients?
Screening is of no benefit if it fails to detect disease that is present (false negative results), if it detects disease that is not present (false positive results), if it detects disease that is indolent and would not ever cause clinical symptoms (overdiagnosis), and if it detects disease for which treatment is not effective or no more effective than it would be if the disease had not been identified until the symptomatic stage.

When Does Screening Harm Patients?
Screening is harmful when patients are given an incorrect diagnosis. False positive results create anxiety and discomfort and often incur risk and cost from additional testing or treatment for a disease which does not exist. False negative results provide reassurance when there actually is a disease present, which can delay truly beneficial diagnosis and treatment. 

Even correct diagnoses can cause harm.9-10The distress associated with a diagnosis of cancer in an asymptomatic patient, for example, is not counterbalanced by any benefit if there is no effective treatment. The patient simply lives longer knowing they have an illness they cannot treat. And overdiagnosis, the correct identification of disease that is non-progressive and does not lead to illness, exposes patients and owners to the risks and costs of the initial diagnosis and any further testing and treatment without any potential benefit from intervention. Patients may perceive a benefit from false positive results or from knowing about and treating indolent disease, but objectively this can only cause harm.11-13

How Do We Evaluate the Risks and Benefits of Screening?
It is rarely possible to know if screening has been beneficial or harmful for a particular individual because the outcome in the absence of testing cannot be known. Patients, pet owners, and clinicians nearly always feel as if testing is worthwhile even when not objective benefit can be demonstrated. True negative and false negative results are always reassuring, and if disease develops later there is rarely any recognition that these results may have delayed identification and treatment of it. Even if a false positive test is later shown to be false by further evaluation, many people experience such relief at the eventual result that they are grateful for the screening even though objectively the cost and discomfort associated with it have no possible benefit. Subjective evaluation of screening, then, nearly always supports it, but this is a limited and unreliable measure of the value of such testing.

Statistical evaluation of specific tests can be useful. The well-known parameters of sensitivity and specificity tell us something about the reliability of tests. However, the parameters of positive and negative predictive (PPV and NPV) value are arguably more important clinically. These are a function not only of the tests but of the prevalence of the disease we are testing for. If the majority of the population does not have the disease (as is usually the case with screening of asymptomatic individuals), the PPV will be quite low and most positive results will be false positives. Since most patients diagnosed through screening don’t actually have that disease they are tested for, the overall risks and costs of screening and follow-up testing or treatment may outweigh the benefits even if some individual patients are helped.14

The most accurate way to determine whether more patients benefit or are harmed by screening is through epidemiologic data regarding specific diseases and the outcome of screening and treatment.1-3,10-11,15Data on large populations has shown, for example, that most prostate cancer detected by PSA testing is nonprogressive. While some individuals do benefit from early detection, statistically many more undergo psychological distress (including a rise in heart attacks and suicide) and physical harm (such as incontinence, impotence, and even death) due to testing and treatment. PSA screening is no longer recommended as widely as it once was because such evidence shows the practice does more harm than good.4,9-10Similar evidence has led to reduced use of mammography and many other screening tests in humans.5, 9-10

Unfortunately, there is little data and awareness of this issue in veterinary medicine, and screening is widely viewed as an unqualified good. For example, the recent AAHA/IDEXX effort to encourage more laboratory testing of asymptomatic individuals never mentions overdiagnosis and suggests that even normal results or abnormal findings of no clinical significance should be “celebrated” and treated as useful information.6Screening is frequently promoted as a marker of high-quality, effective medicine.16-19The financial benefits of screening, to veterinary practices and companies that provide testing services, are also often mentioned as a benefit,6without any discussion about the issue of veterinary healthcare costs and the potential impact of this on availability of care.20-21

There is little evidence that screening improves outcomes such as quality of life or mortality in veterinary patients for most conditions. Research shows that testing of asymptomatic individuals often finds abnormalities and that some of these lead to potentially beneficial intervention.6,9However, few studies have looked at costs and risks of screening or gathered objective data on the balance between these and the potential benefits.

Bottom Line
“All screening programmes do harm; some do good as well, and, of these, some do more good than harm at reasonable cost.” (Gray et al, 2008)22The challenge for veterinary medicine is to recognize the potential harms of screening and to actively collect evidence to identify the risks and benefits of specific tests in specific populations. The current approach of assuming the theoretical benefits of screening must apply and that harms are negligible is not consistent with the evidence from human medicine and not a cost-effective, evidence-based approach for improving the welfare of our patients.

 The Power of Stories
Anecdotes are the primary justification for screening in veterinary medicine. The AAHA/IDEXX protocol, for example, includes a section called “The Power of Stories” which provides anecdotes of patients who benefitted from screening tests. Apart from not being an objective measure of the balance between risks and benefits, anecdotes can just as easily be used to challenge screening as to defend it. Here are two brief examples. 

Case Example: 10 Year-old Whippet
The patient presented for an annual examination and was offered a CBC and chemistry panel. Thrombocytopenia was identified, as well as mild neutropenia, elevated amylase, and decrease AST and CPK. Follow-up testing confirmed thrombocytopenia, and the patient was referred for further testing. Tick-borne disease panel, abdominal ultrasound, and thoracic radiographs were unremarkable. A subsequent CBC was unchanged, and pathology review concluded the findings were likely normal for the individual and breed. Despite the lack of any preceding or subsequent clinical illness, the owner experienced great distress at the possibility of serious illness in her pet, and the patient was exposed to the discomfort of numerous diagnostic procedures at a total cost of $924. 

Case Example: 5 Year-old Labrador Retriever
The patient presented with acute-onset lameness in the left hind leg and no other symptoms. Physical examination identified acute cranial cruciate ligament rupture. Pre-anesthetic chemistry panel revealed moderate elevation of ALT. Abdominal ultrasound identified mildly hypoechoic, indistinct nodular foci in the liver. Ultrasound-guided biopsy identified benign nodular hyperplasia. The patient died of hemorrhage following the biopsy. 

1. Wilson JMG. Jungner G. (1968) Principles and practice of screening for disease. World Health Organization Public Health Papers #34. Geneva, Switzerland.

2. Speechley M. Kunnilathu A. Aluckal E. et al. Screening in Public Health and Clinical Care: Similarities and Differences in Definitions, Types, and Aims – A Systematic Review. Journal of Clinical and Diagnostic Research. 2017;11(3):LE01-LE04.

3. Bulliard JL. Chiolero A. Screening and overdiagnosis: Public health implications. Public Health reviews. 2015:36(8). 

4. Tabayoyong W, Abouassaly R. Prostate Cancer Screening and the Associated Controversy. Surg Clin North Am. 2015 Oct;95(5):1023-39. 

5. Berry DA. Breast cancer screening: controversy of impact. Breast. 2013 Aug;22 Suppl 2:S73-

6. American Animal Hospital Association. Promoting preventative care protocols: Evidence, enactment, and economics. 2018. Accessed September 21, 2018. Available at: https://www.aaha.org/public_documents/professional/resources/promoting_preventive_care_protocols.pdf

7. International Renal Interest Society. IRIS staging of CKD. 2017. Accessed September 21, 2018. Available at: http://www.iris-kidney.com/pdf/IRIS_2017_Staging_of_CKD_09May18.pdf

8. Ross SJ, Osborne CA, Kirk CA, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc. 2006 Sep 15;229(6):949-57.

9. McKenzie, BA. Overdiagnosis. J Amer Vet Med Assoc. 2016;249(8):884-889.

10. Welch HG, Schwartz LM, Woloshin S. Overdiagnosed: mak­ing people sick in pursuit of health. Boston: Beacon Press, 2011.

11. Raffle AE. Gray JAM. Screening: Evidence and Practice. Oxford: Oxford University Press, 2007. 

12. Boone D. Mallett S. Zhu S. et al. Patients’ & Healthcare Professionals’ Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment. PLoS ONE 2017;8(12): e80767. 

13. Brodersen J, Siersma VD. Long-Term Psychosocial Consequences of False-Positive Screening Mammography. Annals of Family Medicine. 2013;11(2):106-115.

14. Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhalation Toxicology. 2014;26(13):811-828. 

15. Gates TJ. Screening for cancer: concepts and controversies. Am Fam Physician. 2014 Nov 1;90(9):625-31.

16. Lewis HB. Healthy pets benefit from blood work. Ban­field Data Savant. Accessed September 21, 2018. Available at: www.banfield.com/getmedia/1216c698-7da1-4899-81a3-24ab549b7a8c/2_1-Healthy-Pets-benefit-from-blood-work.

17. Irwin J. Do tests first: pre-surgical blood work may eliminate variety of surprises. DVM 360 Nov 1, 2003.

18. IDEXX Laboratories. Preanesthetic testing: don’t compro­mise—change happens fast. Accessed September 21, 2018. Available at: www.idexx.com.au/smallanimal/inhouse/preanesthetic-testing.html

19. Ward E. Ask the expert: preanesthetic testing in private prac­tice. NAVC Clinician’s Brief. January 2010. Accessed September 21, 2018. Available at: https://www.cliniciansbrief.com/article/preanesthetic-testing-private-practice

20. LaVallee E, Mueller MK, McCobb E. A Systematic Review of the Literature Addressing Veterinary Care for Underserved Communities. J Appl Anim Welf Sci. 2017 Oct-Dec;20(4):381-394.

21. Stull JW. Shelby J. Bonnett B. et al. Broadening access to veterinary care: Barriers and next steps to providing a spectrum of effective healthcare to our patients. J Amer Vet Med Assoc. 2018. In press

22. Gray JAM, Patnick J, Blanks RG. Maximising benefit and minimising harm of screening. British Medical Journal. 2008;336(7642):480-483.

Posted in Science-Based Veterinary Medicine, Uncategorized | 21 Comments

Should we be Vaccinating Dogs at Acupuncture Points?

A couple of recent articles by acupuncturists have suggested that giving vaccines at acupuncture points may be more effective than giving them in other locations. This is clearly an attempt to demonstrate the serious, scientific legitimacy of acupuncture. However, there are a number of serious problems with these claims and with the studies used to support them. 

Study 1
Jin H, Xu Y, Shi F, Hu S. Vaccination at different anatomic sites induces different levels of the immune responses.Res Vet Sci. 2019;122:50-55. doi:10.1016/j.rvsc.2018.11.005

The Study
This study vaccinated rats with a live attenuated combination vaccine for dogs containing antigens for canine distemper, canine parvovirus, canine parainfluenza, canine adenovirus, and rabies. The rats were injected at several different anatomic locations (see Figure 1). A group of 10 female Rottweiler puppies between 32-36 days old were also vaccinated twice, three weeks apart, first with a modified live distemper/parvo vaccine and then with a modified-live vaccines for distemper, parvovirus, adenovirus, and parainfluenza. These vaccines were given at different locations in different dogs (see Figure 1). 

Figure 1

The study measured blood antibody levels as a marker of vaccine response. The rats were vaccinated twice, 2 weeks apart, and blood was collected at 2, 4, and 6 weeks after the second vaccination. The dogs were vaccinated twice, with different vaccines, three weeks apart. Blood was collected from the dogs 2, 4, and 6 weeks after the second vaccination. The levels of antibodies detected at each time period following vaccination at the different locations in the rats and dogs are shown in Figures 2 and 3.

Figure 2
Figure 3

Analysis of the Study
Methodologically, this study lacks a number of important features to control for error and bias. There was no randomization of subjects, no blinding of investigators or caregivers to the different treatments, and only a small number of dogs of one sex and breed were included. Such controls are especially important given that the study was funded by a veterinary acupuncture group with a clear interest in the outcome. It is also unclear what relevance the immune response of rats to injection with canine vaccines might have to the effect of those vaccines in protecting dogs from infectious diseases.

The dogs in the study were initially vaccinated at about 4 weeks of age, which is earlier than recommended because most puppies will have maternal antibodies at this age that interfere with the effect of vaccination. The second vaccine they received was at about 7 weeks of age, which is still slightly earlier than typically recommended. It is unclear whether these puppies had nursed or had maternal antibodies to begin with, but generally vaccination is done repeatedly between 8 and 16-20 weeks to ensure an adequate immune response. 

It is also unclear whether the differences in antibody levels have any real-world significance. With only a couple of exceptions, the levels were above or below the cutoff for all dogs in all groups at each time point. All dogs achieved antibody levels above the cutoff by about 11 weeks of age, well before the end of the usual vaccine series, so there is little reason to think the differences measured have any implications for susceptibility to disease, which is the import thing in any immunization program. There were also no adverse events for any of the dogs, so there is no reason to think the location of vaccination influences safety or effectiveness of immunization. 

The fact that antibody levels different with the site of vaccination is interesting. There has been some research in humans suggesting that the anatomic location of vaccination can influence the strength of the response.1-2This is suspected to be due to differences in blood supply, fat density, presence of immune surveillance cells, and other such factors. However, what, if anything, this has to do with acupuncture is a different question. For one thing, as I have discussed in detail in the past, there is little compelling evidence that acupuncture points exist at all as distinctive anatomic or functional locations. There is also significant variation in where acupuncturists locate such points, suggesting the concept is more a metaphor than a biological reality. 

In this study, the highest antibody levels were detected at the huohaiacupuncture point (also known as GV 1). This is a sensitive spot between the dorsal edge of the anus and the ventral tail base (see Figure 1). There likely are differences in the activity of the immune system between such a protected spot located close to an obvious source of bacteria and a location like the nape of the neck, a spot fortified against attack with thick skin and subcutaneous fat, little blood supply, and far from any excretory organs. There are plenty of distinctions between such locations that are far more plausible than the mystical notions of energy channels, Ch’i, Yin and Yang, and the other ideas that form the theoretical structure of Traditional Chinese Medicine. Any difference that might be found between the immune response at these spots does not require us to accept the reality of such folk mythology as the only explanation.

Study 2
Perdrizet JA, Shiau D-S, Xie H. The serological response in dogs inoculated with canine distemper virus vaccine at the acupuncture point governing vessel-14: A randomized controlled trialVaccine. 2019;37(13):1889-1896. doi:10.1016/j.vaccine.2018.10.076

The Study
100 client-owned dogs were randomly assigned (though by an odd method with some potential for umasking) to be vaccinated with a modified-live vaccine containing antigens for canine distemper, adenovirus, parvovirus, and parainfluenza at either the side of the neck or at the GV-14 acupuncture point (dorsal midline cranial to the dorsal spinous process of T1). Antibody titers for canine distemper were measured at the time of vaccination and 2 weeks later for all dogs.

Analysis of the Study
The dogs in both groups were vaccinated about a year after previous vaccination, which is earlier than the 3-5 years typically recommended, and both groups had both measurable antibody levels before vaccination and an increase in these levels after vaccination. There was tremendous individual variation in antibody titers and response to vaccination (Figures 4 and 5). Whether there is a consistent and meaningful effect of location of immune response is difficult to tease out of this background variation. The authors did some transformations and various statistical manipulation of the data to identify a statistically significant difference. Whether this is a true difference or a function of the particular study and the methods used is unclear.

Figure 4. Antibody responses to vaccination in different sites
Figure 5. Change in antibody titers after vaccination in different sites.

It is also unclear if there is any real-world difference in the protection against disease between these groups, a fact the authors acknowledge. Even if the location of vaccination predictably influences the magnitude of immune response, most dogs will be protected either way and a small proportion will not be protected either way, so is there any meaningful difference in the chances of dogs becoming ill? That is not a question this study can answer, but given how effective current vaccination is for core infectious diseases, it seems unlikely that changing the location in which we vaccinate is going to protect more dogs.

The authors imply that one reason to determine if vaccination at supposed acupuncture points might be worthwhile is that we could reduce the risks of vaccination if we generated a stronger or more durable response and, presumably, could then vaccinate less. This is implausible. For one thing, the disease they suggest result from vaccination, such as immune-mediated destruction of platelets or red blood cells, have not been consistently or convincingly associated with vaccines.And if we were able to trigger a stronger immune response by vaccinating in a particular location, there is no reason to believe this would not also increase any risks associated with the vaccination response. No adverse events were reported for either group in this study (not surprisingly, since such reactions are uncommon, though it is also possible that dogs with a history of vaccine reactions simply were not included in the study since they may no longer be receiving vaccines). 

General Issues 
These studies do not make a convincing case for vaccinating dogs in supposed acupuncture points. The reasons for this include the following:

  1. The principles of Traditional Chinese Medicineare unscientific folk mythology, and there is no reason to believe any practice guided by these ideas is going to be equal to or superior to practices based on scientific principles.

  2. Despite thousands of years of use, and decades of research, it has not been convincingly shown that so-called acupuncture points exist at all, except as metaphorical concepts. Acupuncturists in different sects identify very different points, and studies show acupuncturists are highly variable and imprecise in their localization of points. No consistent evidence indicates that acupuncture points in general, or the specific points in these studies, have distinctive and relevant anatomic or functional differences from other locations not designated as “points” by the TCM mythology.

  3. The variability in antibody levels and immune response may well be influenced by the location of vaccination. However, any such effect is more likely to be explained by objective and conventional anatomic and functional features of these locations, not by their status as special locations in terms of folk metaphors.

  4. There is great individual variation in antibody levels and immune response to vaccination, and it is unclear whether the statistical differences identified in these studies represent real differences, study artefacts, or normal variability. There is a growing recognition that statistical significance testing is misused in medical research and readily creates the impression of meaningful biological difference where none exists. This awareness has led to calls from statisticians and researchers to abandon the practice and emphasize more meaningful measures of effect in research studies.

  5. Even if it were established that there were true differences between the groups in these studies, from whatever cause, it has yet to be established that these have any real-world significance in terms of protection from disease or safety. Current vaccination practice are incredibly safe and effective, and while improvement is always desirable, the small differences seen in these studies are unlikely to have any implications for the actual health of patients. Certainly, nothing in this research suggests the locations chosen by the authors are safer or more effective at presenting disease than current locations typically used.

  6. From the practical perspective of a clinician actually treating dogs, I can tell you that vaccinating routinely at GV-1 (just above the anus) is going to be far more painful and difficult than current locations. Without a large, proven benefit to doing so, it makes no sense to subject patients or staff to this practice. 

Interestingly, the least antibody response seen in the Jin study was at a location very close to the GV-14 point used in the Perdrizet study. While I’m sure the authors would argue that these points are not comparable because of the precise localization of acupuncture point, again the research indicates that such points are in fact quite variable and imprecise, so to a small extent these studies actually contradict one another in terms of the effect of vaccination over the shoulders.

Bottom Line
There is no plausible reason to think that vaccinating dogs at supposed acupuncture points, if these even exist, will improve the protection from disease conveyed by vaccination or will reduce the risks of vaccinating.


  1. Jin H, Xu Y, Shi F, Hu S. Vaccination at different anatomic sites induces different levels of the immune responses. Res Vet Sci. 2019;122:50-55. doi:10.1016/j.rvsc.2018.11.005

  2. Shaw FE, Guess HA, Roets JM, et al. Effect of anatomic injection site, age and smoking on the immune response to hepatitis B vaccination. Vaccine. 1989;7(5):425-430. http://www.ncbi.nlm.nih.gov/pubmed/2530717. Accessed April 8, 2019.
Posted in Acupuncture | 6 Comments

Herbalists Petition for Specialty Recognition is Rejected

I recently updated my coverage of attempts by the American College of Veterinary Botanical Medicine (ACVBM) to attain specialty recognition, and explained why I am opposed to this effort. The deliberations and decisions of the American Board of Veterinary Specialties (ABVS) are shrouded in mystery and seldom discussed publicly, but I have been able to confirm that the ABVS has rejected the ACVBM petition. While I am hopeful that appropriate scientific study will find useful treatments buried in the pile of accumulated tradition and anecdote that currently makes up veterinary herbal medicine, I believe the ACVBM is not the organization to lead this effort, and I think the ABVS decision is in the best interests of animal patients.

Posted in Herbs and Supplements | 5 Comments

A Detailed, Evidence-based response to Petco’s Ban on “Artificial” Food Ingredients

Here is an article from Veterinary Practice News responding to the ridiculous marketing ploy by Petco declaring a ban on “artificial” food ingredients.

Since the late 1980s, individuals and organizations have been trying to warn the public about a deadly chemical known as DHMO. Though widely used in the home and in commercial settings, including the healthcare industry, this substance has been shown to cause severe lung damage and even death if inhaled in small quantities. Hundreds of thousands of people die annually from this cause.1

DHMO can also cause electrolyte disturbances and potentially fatal neurologic symptoms when taken orally, and it can cause severe burns and even explosions when heated.2A number of surveys have found high levels of support for banning DHMO, and elected officials in several countries have explored taking such action, but DHMO remains ubiquitous.3,4

Given the obvious dangers of this chemical, why do public health agencies not take action to restrict it? It is possible that funding and political influence from industry impedes regulatory action. However, it is more likely that governments have chosen not to ban DHMO because it is essential for life. Most people are surprised to learn this until they recognize the non-technical name for this chemical—water.

The campaign against DHMO (dihydrogen monoxide) has been used as a humorous illustration of the problem of chemophobia or chemonoia. These terms refer to the potent and widespread fear of anything labeled a “chemical.”5–7Nonscientists often assume that chemicals are inherently dangerous, even though the word properly refers to nearly every substance we encounter in daily life, from the deadliest poison to the basic necessities of life and even the materials that makes up our own bodies.

A concept integral to chemophobia is the Appeal to Nature Fallacy, the misconception that substances which occur naturally are inherently healthy and safe while those produced by humans, even if chemically identical to natural substances, are dangerous. Of course, it is easy to find examples that belie this notion. Nothing could be more natural than the E. colior Salmonella. Radioactive uranium, asbestos, and cyanide are completely natural. 

In contrast, the vaccines which have eliminated smallpox and polio are undeniably artificial. Antibiotics, synthetic vitamin supplements, blood transfusions, organ transplants, prosthetic limbs, insulin for diabetics, and even such simple and unheralded public health technologies as indoor plumbing and toilet paper have saved lives and reduced suffering for millions. Yet these are not “natural” in the usual sense of the word. 

Unfortunately, chemophobia and the Appeal to Nature Fallacy are widespread, and they often motivate pet care decisions. Some organizations and individuals take advantage of this by offering “natural” products or therapies and warning of the dangers of “chemicals” and anything “artificial.” A recent high-profile example of this exploitation of chemophobia is the announcement by Petco that the company “will not sell food and treats containing artificial colors, flavors and preservatives for dogs and cats.”8

The company’s public relations materials call this decision “a major step forward for pets” on “a momentous day.”8Petco effectively declares itself the arbiter of what constitutes healthy nutrition, even going so far as offering to “help pet parents affected by such a change to safely transition to a new food or brand that we believe is healthier for their pet” if customers are no longer able to buy a food they have been using.8Even though regulatory agencies and experts around the world have judged the additives on Petco’s list to be safe, the company has decided it knows better. 

The dramatic rhetoric in the Petco press materials may serve the purpose of creating a positive and profitable image for the company, but it obscures the danger of a marketing strategy that caters to unscientific reasoning and mostly unfounded fears. There is little in the way of scientific evidence, or even logical consistency, behind the Petco blacklist.9

For example, many of the “artificial” flavors and preservatives on the list occur naturally (see Table 1). Of course, the fact that these chemicals occur in nature doesn’t make them safe, just as flavors and preservatives are not necessarily unsafe if produced synthetically. However, the fact that Petco is banning naturally occurring substances for being “artificial” exposes the inconsistent logic behind this blacklist.

The health risks of most substances are related to the dose and route of exposure. And the risk of any substance should always be considered in relation to its benefits. Water is unsafe to drink only in very large quantities, but it is unsafe to breathe in even small amounts. It is also essential for life, taken at appropriate doses and by the appropriate route. The same logic, informed by scientific evidence concerning risks and benefits, should be applied to food additives, but Petco does not use this approach. 

Some of the substances on the list have no clear health implications. The color additives, for example, are almost certainly safe, but they serve no nutritional or health purpose.10,11,20–25,12–19These chemicals are added to pet food to appeal to the emotions and aesthetics of pet owners. While they serve no health-related purpose, banning these compounds is itself a way of appealing to the emotions of owners and their irrational fears, and there is no sound reason to believe this will benefit the health of pets.

For other items on the list, the impact of discouraging their use is less clear. Flavorings, for example, make nutritious and affordable commercial foods more palatable. Removing them may make it harder to provider appropriate nutrition to pets, and it may encourage owners to switch to homemade or other alternative diets that are often nutritionally inferior.26–31

The most clearly beneficial chemicals on the blacklist are the preservatives. Preventing spoilage, pathogen growth, and loss of nutrients in pet food is critical to providing healthy diets. In the absence of convincing evidence that commonly used and legally approved preservatives are actually harmful, removing them can only lead to less safe and healthy food for pets.

The evidence of health risks for most of the additives on the list is weak and based primarily on in vitroand lab animal studies that do not reliably predict the effects of normal use in pet foods. Most of these additives have been used for decades and reviewed periodically by regulators with no convincing evidence of negative health effects in humans or pets. Some may have risks that warrant removing them from use, but the evidence to make this case is lacking.

One can make the argument, of course, that any substance which has shown any hint of toxicity in lab animal studies ought to be avoided. There is little evidence, however, that this precautionary approach actually reduces harm. If the substances that are abandoned are actually safe, then there is no benefit. And there is always the potential that new, less thoroughly tested alternatives may have greater risks, even if they are “natural.”32

There is even evidence that some of the additives on the Petco list may actually have health benefits (see references from Table 1). Many have antiseptic, anti-inflammatory, anti-neoplastic, and antioxidant activity or other potentially beneficial uses. While the evidence for these effects is weak and based mostly on in vitroand lab animal studies, this is no less convincing than the evidence for negative health effects Petco has used to justify banning these compounds. 

Irrational and unscientific reasoning is not likely to lead to good healthcare choices. Unjustified fear of grains has led to grain-free diets making up about 25% of the dog food market. There is no reason to believe these diets have health benefits, and there are beginning to be signs that feeding these diets may be harming dogs.33–35The same reasoning that underlies this blacklist has also led Petco to sell raw diets, which have well-established health risks,28,36–42and to offer worthless homeopathic remedies43–47that pet owners may mistakenly substitute for effective, science-based medical treatment.  

The best way to protect our pets’ health is to rely on sound scientific evidence to help us weigh the risks and benefits of the food and medicine we provide, not to cater to irrational fears like chemophobia and meaningless distinctions such as “natural” and artificial.”  Table 1 provides a partial list of the sources, regulatory approvals, and evidence for safety and potentially beneficial effects of the items on the Petco blacklist. This is not a comprehensive review, simply an illustration that the items on this list are often “natural,” are judge by government experts around the world to be safe as used in food for humans and animals, and may have beneficial uses that offset any risk they may present. 

Veterinarians have a responsibility to support and educate pet owners and to challenge unscientific, fear-based marketing ploys like the Petco blacklist. The movement towards dangerous “natural” practices like feeding raw diets and avoiding vaccination is a real threat to animal welfare, and it is exacerbated by companies seeking market advantage through feeding and capitalizing on misconceptions and fear. 


1.        World Health Organization. Drowning.; 2018. https://www.who.int/news-room/fact-sheets/detail/drowning. Accessed December 24, 2018.

2.        DHMO.ORG. Facts About Dihydrogen Monoxide. http://www.dhmo.org/facts.html. Published 2018. Accessed December 24, 2018.

3.        DHMO.ORG Research Division. DHMO Research Reports. http://www.dhmo.org/research.html. Published 2008. Accessed December 24, 2018.

4.        Stuff.co.nz. National MP falls victim to water hoax. Stuff. http://www.stuff.co.nz/national/politics/38005/National-MP-falls-victim-to-water-hoax. Published 2009. Accessed December 24, 2018.

5.        Robson D. Chemonoia: The fear blinding our minds to real dangers. BBC FUture.

6.        Francl M. How to counteract chemophobia. Nat Chem. 2013;5(6):439-440. doi:10.1038/nchem.1661

7.        Ropeik D. On the roots of, and solutions to, the persistent battle between “chemonoia” and rationalist denialism of the subjective nature of human cognition. Hum Exp Toxicol. 2015;34(12):1272-1278. doi:10.1177/0960327115603592

8.        Petco. Petco First and Only Major Retailer of Pet Food to Not Sell Food and Treats with Artificial Ingredients. PR Newswire. https://www.prnewswire.com/news-releases/petco-first-and-only-major-retailer-of-pet-food-to-not-sell-food-and-treats-with-artificial-ingredients-300748831.html. Published 2018. Accessed December 24, 2018.

9.        Ingredients Which Do Not Meet Petco’s New Nutritional Standards. https://www.petco.com/shop/en/petcostore/c/betternutrition-ingredients. Published 2018. Accessed December 24, 2018.

10.      Bastaki M, Farrell T, Bhusari S, Bi X, Scrafford C. Estimated daily intake and safety of FD&C food-colour additives in the US population. Food Addit Contam Part A. 2017;34(6):891-904. doi:10.1080/19440049.2017.1308018

11.      Bastaki M, Farrell T, Bhusari S, Pant K, Kulkarni R. Lack of genotoxicity in vivo for food color additive Allura Red AC. Food Chem Toxicol. 2017;105:308-314. doi:10.1016/j.fct.2017.04.037

12.      Bastaki M, Farrell T, Bhusari S, Pant K, Kulkarni R. Lack of genotoxicity in vivo for food color additive Tartrazine. Food Chem Toxicol. 2017;105:278-284. doi:10.1016/j.fct.2017.04.034

13.      Amchova P, Kotolova H, Ruda-Kucerova J. Health safety issues of synthetic food colorants. Regul Toxicol Pharmacol. 2015;73(3):914-922. doi:10.1016/j.yrtph.2015.09.026

14.      Oplatowska-Stachowiak M, Elliott CT. Food colors: Existing and emerging food safety concerns. Crit Rev Food Sci Nutr. 2017;57(3):524-548. doi:10.1080/10408398.2014.889652

15.      Younes M, Aggett P, Aguilar F, et al. Evaluation of four new studies on the potential toxicity of titanium dioxide used as a food additive (E 171). EFSA J. 2018;16(7). doi:10.2903/j.efsa.2018.5366

16.      European Food Safety Authority (EFSA). Food colours: titanium dioxide marks re-evaluation milestone |. http://www.efsa.europa.eu/en/press/news/160914. Published 2016. Accessed December 25, 2018.

17.      Food and Drug Administration (FDA). Titanium Dioxide.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=73.575. Accessed December 25, 2018.

18.      European Food Safety Authority (EFSA). Food Colours. http://www.efsa.europa.eu/en/topics/topic/food-colours. Published 2016. Accessed December 25, 2018.

19.      Food Standards Australia New Zealand. Food Colours. http://www.foodstandards.gov.au/consumer/additives/foodcolour/pages/default.aspx. Published 2012. Accessed December 25, 2018.

20.      Food Standards Australia New Zealand (FSANZ). Supplementary food colours report. http://www.foodstandards.gov.au/science/surveillance/pages/supplementaryfoodcol5571.aspx. Published 2012. Accessed December 25, 2018.

21.      FDA. Overview of Food Ingredients, Additives & Colors. US Food Drug Adm. 2010. https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm094211.htm#qahyper. Accessed December 25, 2018.

22.      Center for Food Safety and Applied Nutrition F. Food Additives & Ingredients – Color Additives Questions and Answers for Consumers. https://www.fda.gov/food/ingredientspackaginglabeling/foodadditivesingredients/ucm488219.htm. Accessed December 25, 2018.

23.      Laflamme D, Izquierdo O, Eirmann L, Binder S. Myths and Misperceptions About Ingredients Used in Commercial Pet Foods. Vet Clin North Am Small Anim Pract. 2014;44(4):689-698. doi:10.1016/j.cvsm.2014.03.002

24.      Wortinger A. Nutritional Myths. J Am Anim Hosp Assoc. 2005;41(4):273-276. doi:10.5326/0410273

25.      Case LP, Daristotle L, Hayek L, Foess Raasch M. Common Nutrition Myths and Feeding Practices. In: Canine and Feline Nutrition. 3rd ed. Maryland Hwights, MO: Mosby Elsevier; 2010:277-294.

26.      Weeth LP. Focus on nutrition: Home-prepared diets for dogs and cats. Compend Contin Educ Vet. 2013;35(3):E3. http://www.ncbi.nlm.nih.gov/pubmed/23532921. Accessed October 28, 2018.

27.      Streiff EL, Zwischenberger B, Butterwick RF, Wagner E, Iben C, Bauer JE. A Comparison of the Nutritional Adequacy of Home-Prepared and Commercial Diets for Dogs. J Nutr. 2002;132(6):1698S-1700S. doi:10.1093/jn/132.6.1698S

28.      Schlesinger DP, Joffe DJ. Raw food diets in companion animals: a critical review. Can Vet J = La Rev Vet Can. 2011;52(1):50-54. http://www.ncbi.nlm.nih.gov/pubmed/21461207. Accessed October 28, 2018.

29.      Streiff EL, Zwischenberger B, Butterwick RF, Wagner E, Iben C, Bauer JE. A comparison of the nutritional adequacy of home-prepared and commercial diets for dogs. J Nutr. 2002;132(6 Suppl 2):1698S-700S. doi:10.1093/jn/132.6.1698S

30.      Stockman J, Fascetti AJ, Kass PH, Larsen JA. Evaluation of recipes of home-prepared maintenance diets for dogs. J Am Vet Med Assoc. 2013;242(11):1500-1505. doi:10.2460/javma.242.11.1500

31.      Hutchinson D, Freeman LM, McCarthy R, Anastasio J, Shaw SP, Sutherland-Smith J. Seizures and severe nutrient deficiencies in a puppy fed a homemade diet. J Am Vet Med Assoc. 2012;241(4):477-483. doi:10.2460/javma.241.4.477

32.      Simon JE, Decker EA, Ferruzzi MG, et al. Establishing Standards on Colors from Natural Sources. J Food Sci. 2017;82(11):2539-2553. doi:10.1111/1750-3841.13927

33.      Freeman LM, Stern JA, Fries R, Adin DB, Rush JE. Diet-associated dilated cardiomyopathy in dogs: what do we know? J Am Vet Med Assoc. 2018;253(11):1390-1394. doi:10.2460/javma.253.11.1390

34.      Kaplan JL, Stern JA, Fascetti AJ, et al. Taurine deficiency and dilated cardiomyopathy in golden retrievers fed commercial diets. Loor JJ, ed. PLoS One. 2018;13(12):e0209112. doi:10.1371/journal.pone.0209112

35.      Adin D, DeFrancesco TC, Keene B, et al. Echocardiographic phenotype of canine dilated cardiomyopathy differs based on diet type. J Vet Cardiol. 2019;21:1-9. doi:10.1016/J.JVC.2018.11.002

36.      Freeman LM, Chandler ML, Hamper BA, Weeth LP. Current knowledge about the risks and benefits of raw meat-based diets for dogs and cats. J Am Vet Med Assoc. 2013;243(11):1549-1558. doi:10.2460/javma.243.11.1549

37.      Health England P. Investigation into an Outbreak of Shiga Toxin Producing Escherichia Coli.; 2017. www.facebook.com/PublicHealthEngland. Accessed December 6, 2018.

38.      Chengappa MM, Staats J, Oberst RD, Gabbert NH, McVey S. Prevalence of Salmonellain Raw Meat used in Diets of Racing Greyhounds. J Vet Diagnostic Investig. 1993;5(3):372-377. doi:10.1177/104063879300500312

39.      Finley R, Ribble C, Aramini J, et al. The risk of salmonellae shedding by dogs fed Salmonella-contaminated commercial raw food diets. Can Vet J = La Rev Vet Can. 2007;48(1):69-75. http://www.ncbi.nlm.nih.gov/pubmed/17310625. Accessed October 27, 2018.

40.      Joffe DJ, Schlesinger DP. Preliminary assessment of the risk of Salmonella infection in dogs fed raw chicken diets. Can Vet J = La Rev Vet Can. 2002;43(6):441-442. http://www.ncbi.nlm.nih.gov/pubmed/12058569. Accessed October 27, 2018.

41.      Weese JS, Rousseau J, Arroyo L. Bacteriological evaluation of commercial canine and feline raw diets. Can Vet J = La Rev Vet Can. 2005;46(6):513-516. http://www.ncbi.nlm.nih.gov/pubmed/16048011. Accessed October 27, 2018.

42.      Strohmeyer RA, Morley PS, Hyatt DR, Dargatz DA, Scorza AV, Lappin MR. Evaluation of bacterial and protozoal contamination of commercially available raw meat diets for dogs. J Am Vet Med Assoc. 2006;228(4):537-542. doi:10.2460/javma.228.4.537

43.      Ernst E. Homeopathy – The Undiluted Facts. Cham: Springer International Publishing; 2016. doi:10.1007/978-3-319-43592-3

44.      Ernst E. A systematic review of systematic reviews of homeopathy. Br J Clin Pharmacol. 2002;54(6):577-582. http://www.ncbi.nlm.nih.gov/pubmed/12492603. Accessed November 12, 2018.

45.      Shang A, Huwiler-Müntener K, Nartey L, et al. Are the clinical effects of homoeopathy placebo effects? Comparative study of placebo-controlled trials of homoeopathy and allopathy. Lancet (London, England). 2005;366(9487):726-732. doi:10.1016/S0140-6736(05)67177-2

46.      Ernst E, Pittler MH. Re-analysis of previous meta-analysis of clinical trials of homeopathy. J Clin Epidemiol. 2000;53(11):1188. http://www.ncbi.nlm.nih.gov/pubmed/11186614. Accessed November 12, 2018.

47.      Ernst E. Classical homoeopathy versus conventional treatments: a systematic review. 1999. https://www.ncbi.nlm.nih.gov/books/NBK67846/. Accessed November 12, 2018.

48.      Feron VJ, Til HP, de Vrijer F, Woutersen RA, Cassee FR, van Bladeren PJ. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutat Res. 259(3-4):363-385. http://www.ncbi.nlm.nih.gov/pubmed/2017217. Accessed December 25, 2018.

49.      ACETALDEHYDE WORKING GROUP Comments on the CLH Report on Acetaldehyde; Proposal for Harmonised Classification and Labeling (June 2015). https://echa.europa.eu/documents/10162/b9885f2c-b491-4ad4-8900-8cba349b15a0. Accessed December 25, 2018.

50.      Evaluation Report of Food Additives Acetaldehyde Food Safety Commission Evaluation Results on the Health Risk Assessment of Acetaldehyde as Food Additive.; 2005. http://www.fsc.go.jp/english/evaluationreports/foodadditive/acetaldehyde_report.pdf. Accessed December 25, 2018.

51.      Food and Drug Administration (FDA). Substances Generally Recognized as Safe.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=182.60. Accessed December 25, 2018.

52.      World Health Organization (WHO). Evaluations of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). http://apps.who.int/food-additives-contaminants-jecfa-database/search.aspx. Published 2017. Accessed December 25, 2018.

53.      V. V. The Asphyxiating and Exsanguinating Death of President George Washington. Perm J. 2004;8(2):2002-2005.

54.      Aguilar F, Nybro Autrup H, Barlow S, et al. Flavouring Group Evaluation 11, Revision 1 (FGE.11Rev1) 1 Aliphatic Dialcohols, Diketones, and Hydroxyketones from Chemical Group 10 Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) PANEL MEMBERS. Vol 493.; 2008. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/493.pdf. Accessed December 25, 2018.

55.      Xiao Z, Lu JR. Generation of Acetoin and Its Derivatives in Foods. 2014. doi:10.1021/jf5013902

56.      Almodares A, Ranjbar M, Hadi MR. Effects of nitrogen treatments and harvesting stages on the aconitic acid, invert sugar and fiber in sweet sorghum cultivars. J Environ Biol. 2010;31(6):1001-1005. http://www.ncbi.nlm.nih.gov/pubmed/21506489. Accessed December 25, 2018.

57.      Food and Drug Administration (FDA). Aconitic Acid.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1007. Accessed December 25, 2018.

58.      Aprotosoaie AC, Costache I-I, Miron A. Anethole and Its Role in Chronic Diseases. In: Advances in Experimental Medicine and Biology. Vol 929. ; 2016:247-267. doi:10.1007/978-3-319-41342-6_11

59.      Aquilina G, Bories G, Chesson A, et al. Scientific Opinion on the safety and efficacy of allylhydroxybenzenes (chemical group 18) when used as flavourings for all animal species 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). EFSA J. 2011;9(12):2440. doi:10.2903/j.efsa.2011.2440

60.      Kim KY, Lee HS, Seol GH. Anti-inflammatory effects of trans -anethole in a mouse model of chronic obstructive pulmonary disease. Biomed Pharmacother. 2017;91:925-930. doi:10.1016/j.biopha.2017.05.032

61.      Scott HR, Scott LE. Process of treating nut kernels to produce food ingredients. July 1920. https://patents.google.com/patent/US1416128. Accessed December 25, 2018.

62.      Adams TB, Cohen SM, Doull J, et al. The FEMA GRAS assessment of benzyl derivatives used as flavor ingredients. Food Chem Toxicol. 2005;43(8):1207-1240. doi:10.1016/J.FCT.2004.11.014

63.      da Silva DS, da Silva CEH, Soares MSP, et al. Thiazolidin-4-ones from 4-(methylthio)benzaldehyde and 4-(methylsulfonyl)benzaldehyde: Synthesis, antiglioma activity and cytotoxicity. Eur J Med Chem. 2016;124:574-582. doi:10.1016/j.ejmech.2016.08.057

64.      Jang TY, Park C-S, Kim K-S, Heo M-J, Kim YH. Benzaldehyde suppresses murine allergic asthma and rhinitis. Int Immunopharmacol. 2014;22(2):444-450. doi:10.1016/j.intimp.2014.07.029

65.      Final Report on the Safety Assessment of Benzaldehyde1. Int J Toxicol. 2006;25(1_suppl):11-27. doi:10.1080/10915810600716612

66.      Heidor R, Ortega JF, de Conti A, Ong TP, Moreno FS. Anticarcinogenic actions of tributyrin, a butyric acid prodrug. Curr Drug Targets. 2012;13(14):1720-1729. http://www.ncbi.nlm.nih.gov/pubmed/23140283. Accessed December 25, 2018.

67.      Sossai P. Butyric acid: what is the future for this old substance? Swiss Med Wkly. 2012;142:w13596. doi:10.4414/smw.2012.13596

68.      Manrique Vergara D, González Sánchez ME. Ácidos grasos de cadena corta (ácido butírico) y patologías intestinales. Nutr Hosp. 2017;34(4):58-61. doi:10.20960/nh.1573

69.      McNabney SM, Henagan TM. Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance. Nutrients. 2017;9(12). doi:10.3390/nu9121348

70.      Ayd?n E, Türkez H, Kele? MS. Potential anticancer activity of carvone in N2a neuroblastoma cell line. Toxicol Ind Health. 2015;31(8):764-772. doi:10.1177/0748233713484660

71.      Souza FVM, da Rocha MB, de Souza DP, Marçal RM. (?)-Carvone: Antispasmodic effect and mode of action. Fitoterapia. 2013;85:20-24. doi:10.1016/j.fitote.2012.10.012

72.      Muruganathan U, Srinivasan S. Beneficial effect of carvone, a dietary monoterpene ameliorates hyperglycemia by regulating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats. Biomed Pharmacother. 2016;84:1558-1567. doi:10.1016/j.biopha.2016.11.025

73.      Nogoceke FP, Barcaro IMR, de Sousa DP, Andreatini R. Antimanic-like effects of (R)-(?)-carvone and (S)-(+)-carvone in mice. Neurosci Lett. 2016;619:43-48. doi:10.1016/j.neulet.2016.03.013

74.      de Carvalho CCCR, da Fonseca MMR. Carvone: Why and how should one bother to produce this terpene. Food Chem. 2006;95(3):413-422. doi:10.1016/J.FOODCHEM.2005.01.003

75.      Zhu R, Liu H, Liu C, et al. Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety. Pharmacol Res. 2017;122:78-89. doi:10.1016/j.phrs.2017.05.019

76.      Chen B-J, Fu C-S, Li G-H, et al. Cinnamaldehyde Analogues as Potential Therapeutic Agents. Mini Rev Med Chem. 2017;17(1):33-43. http://www.ncbi.nlm.nih.gov/pubmed/26791737. Accessed December 25, 2018.

77.      Friedman M. Chemistry, Antimicrobial Mechanisms, and Antibiotic Activities of Cinnamaldehyde against Pathogenic Bacteria in Animal Feeds and Human Foods. J Agric Food Chem. 2017;65(48):10406-10423. doi:10.1021/acs.jafc.7b04344

78.      Shreaz S, Wani WA, Behbehani JM, et al. Cinnamaldehyde and its derivatives, a novel class of antifungal agents. Fitoterapia. 2016;112:116-131. doi:10.1016/j.fitote.2016.05.016

79.      Pérez Zamora C, Torres C, Nuñez M. Antimicrobial Activity and Chemical Composition of Essential Oils from Verbenaceae Species Growing in South America. Molecules. 2018;23(3):544. doi:10.3390/molecules23030544

80.      Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC) on a Request from the Commission Related to Flavouring Group Evaluation 23: Aliphatic, Alicyclic and Aromatic Ethers Including Anisole Derivatives From Chemical Groups 15, 16 and 26 (Commission Regulation (EC) No.; 1565. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/417.pdf. Accessed December 25, 2018.

81.      Patel S. Plant essential oils and allied volatile fractions as multifunctional additives in meat and fish-based food products: a review. Food Addit Contam Part A. 2015;32(7):1049-1064. doi:10.1080/19440049.2015.1040081

82.      Liu K, Chen Q, Liu Y, Zhou X, Wang X. Isolation and Biological Activities of Decanal, Linalool, Valencene, and Octanal from Sweet Orange Oil. J Food Sci. 2012;77(11):C1156-C1161. doi:10.1111/j.1750-3841.2012.02924.x

83.      Laribi B, Kouki K, M’Hamdi M, Bettaieb T. Coriander (Coriandrum sativum L.) and its bioactive constituents. Fitoterapia. 2015;103:9-26. doi:10.1016/j.fitote.2015.03.012

84.      EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). Scientific Opinion on the safety and efficacy of straight-chain primary aliphatic alcohols/aldehydes/acids, acetals and esters with esters containing saturated alcohols and acetals containing saturated aldehydes (chemical group 1) when used as flavourings. EFSA J. 2013;11(4):3169.

85.      Chhikara N, Kour R, Jaglan S, Gupta P, Gat Y, Panghal A. Citrus medica: nutritional, phytochemical composition and health benefits – a review. Food Funct. 2018;9(4):1978-1992. doi:10.1039/c7fo02035j

86.      Dunnington D, Butterworth KR, Gaunt IF, Mason PL, Evans JG, Gangolli SD. Long-term toxicity study of ethyl methylphenylglycidate (strawberry aldehyde) in the rat. Food Cosmet Toxicol. 1981;19:691-699. doi:10.1016/0015-6264(81)90522-8

87.      Khalil AA, Rahman U ur, Khan MR, Sahar A, Mehmood T, Khan M. Essential oil eugenol: sources, extraction techniques and nutraceutical perspectives. RSC Adv. 2017;7(52):32669-32681. doi:10.1039/C7RA04803C

88.      Flavouring Group Evaluation 60 (FGE.60) 1?: Consideration of Eugenol and Related Hydroxyallylbenzene Derivatives Evaluated by JECFA (65 Th Meeting) Structurally Related to Ring-Substituted Phenolic Substances Evaluated by EFSA in FGE.22 (2006) Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC). http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620772628.htm. Accessed December 25, 2018.

89.      Hu Q, Zhou M, wei S. Progress on the Antimicrobial Activity Research of Clove Oil and Eugenol in the Food Antisepsis Field. J Food Sci. 2018;83(6):1476-1483. doi:10.1111/1750-3841.14180

90.      Api AM, Belsito D, Bhatia S, et al. RIFM fragrance ingredient safety assessment, Eugenol, CAS Registry Number 97-53-0. Food Chem Toxicol. 2016;97:S25-S37. doi:10.1016/j.fct.2015.12.013

91.      Marchese A, Barbieri R, Coppo E, et al. Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint. Crit Rev Microbiol. 2017;43(6):668-689. doi:10.1080/1040841X.2017.1295225

92.      Fujisawa S, Murakami Y. Eugenol and Its Role in Chronic Diseases. In: Advances in Experimental Medicine and Biology. Vol 929. ; 2016:45-66. doi:10.1007/978-3-319-41342-6_3

93.      Food and Drug Administration. CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1257. Accessed December 25, 2018.

94.      Fragrance raw materials monographs: Geranyl acetate. Food Cosmet Toxicol. 1974;12(7-8):885-886. doi:10.1016/0015-6264(74)90167-9

95.      Seebaluck R, Gurib-Fakim A, Mahomoodally F. Medicinal plants from the genus Acalypha (Euphorbiaceae)–A review of their ethnopharmacology and phytochemistry. J Ethnopharmacol. 2015;159:137-157. doi:10.1016/j.jep.2014.10.040

96.      Qi F, Yan Q, Zheng Z, Liu J, Chen Y, Zhang G. Geraniol and geranyl acetate induce potent anticancer effects in colon cancer Colo-205 cells by inducing apoptosis, DNA damage and cell cycle arrest. J BUON. 23(2):346-352. http://www.ncbi.nlm.nih.gov/pubmed/29745075. Accessed December 25, 2018.

97.      National Toxicology Program. NTP Carcinogenesis Studies of Food Grade Geranyl Acetate (71% Geranyl Acetate, 29% Citronellyl Acetate) (CAS No. 105-87-3) in F344/N Rats and B6C3F1 Mice (Gavage Study). Natl Toxicol Program Tech Rep Ser. 1987;252:1-162. http://www.ncbi.nlm.nih.gov/pubmed/12748693. Accessed December 25, 2018.

98.      Heidor R, Ortega JF, de Conti A, Ong TP, Moreno FS. Anticarcinogenic actions of tributyrin, a butyric acid prodrug. Curr Drug Targets. 2012;13(14):1720-1729. http://www.ncbi.nlm.nih.gov/pubmed/23140283. Accessed December 26, 2018.

99.      Bedford A, Gong J. Implications of butyrate and its derivatives for gut health and animal production. Anim Nutr. 2018;4(2):151-159. doi:10.1016/J.ANINU.2017.08.010

100.    Kuefer R, Hofer MD, Altug V, et al. Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer. Br J Cancer. 2004;90(2):535-541. doi:10.1038/sj.bjc.6601510

101.    Kang SN, Lee E, Lee M-K, Lim S-J. Preparation and evaluation of tributyrin emulsion as a potent anti-cancer agent against melanoma. Drug Deliv. 2011;18(2):143-149. doi:10.3109/10717544.2010.522610

102.    Cresci GA, Glueck B, McMullen MR, Xin W, Allende D, Nagy LE. Prophylactic tributyrin treatment mitigates chronic-binge ethanol-induced intestinal barrier and liver injury. J Gastroenterol Hepatol. 2017;32(9):1587-1597. doi:10.1111/jgh.13731

103.    Aquilina G, Bach A, Bampidis V, et al. Scientific Opinion on the safety and efficacy of branched-chain primary aliphatic alcohols/aldehydes/acids, acetals and esters with esters containing branched-chain alcohols and acetals containing branched-chain aldehydes (chemical group 2) when used as flavourings for all animal species 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP). EFSA J. 2012;10(10):2927. doi:10.2903/j.efsa.2012.2927

104.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21. 21CFR184.1903; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1903. Accessed December 26, 2018.

105.    Sun J. D-Limonene: safety and clinical applications. Altern Med Rev. 2007;12(3):259-264. http://www.ncbi.nlm.nih.gov/pubmed/18072821. Accessed December 26, 2018.

106.    Vieira AJ, Beserra FP, Souza MC, Totti BM, Rozza AL. Limonene: Aroma of innovation in health and disease. Chem Biol Interact. 2018;283:97-106. doi:10.1016/j.cbi.2018.02.007

107.    Ravichandran C, Badgujar PC, Gundev P, Upadhyay A. Review of toxicological assessment of d-limonene, a food and cosmetics additive. Food Chem Toxicol. 2018;120:668-680. doi:10.1016/j.fct.2018.07.052

108.    Kim YW, Kim MJ, Chung BY, et al. Safety evaluation and risk assessment of D-limonene. J Toxicol Environ Heal – Part B Crit Rev. 2013;16(1):17-38. doi:10.1080/10937404.2013.769418

109.    Scientific Opinion on the safety and efficacy of aliphatic and aromatic hydrocarbons (chemical group 31) when used as flavourings for all animal species; Scientific Opinion on the safety and efficacy of aliphatic and aromatic hydrocarbons (chemical group 31) when used as flavourings for all animal species. EFSA J. 2015;13(3):4053. doi:10.2903/j.efsa.2015.4053

110.    Pereira I, Severino P, Santos AC, Silva AM, Souto EB. Linalool bioactive properties and potential applicability in drug delivery systems. Colloids Surfaces B Biointerfaces. 2018;171:566-578. doi:10.1016/j.colsurfb.2018.08.001

111.    Seol G-H, Kang P, Lee HS, Seol GH. Antioxidant activity of linalool in patients with carpal tunnel syndrome. BMC Neurol. 2016;16(1):17. doi:10.1186/s12883-016-0541-3

112.    de Oliveira Lima MI, Araújo de Medeiros AC, Souza Silva KV, Cardoso GN, de Oliveira Lima E, de Oliveira Pereira F. Investigation of the antifungal potential of linalool against clinical isolates of fluconazole resistant Trichophyton rubrum. J Mycol Med. 2017;27(2):195-202. doi:10.1016/j.mycmed.2017.01.011

113.    Iwasaki K, Zheng Y-W, Murata S, et al. Anticancer effect of linalool viacancer-specific hydroxyl radical generation in human colon cancer. World J Gastroenterol. 2016;22(44):9765. doi:10.3748/wjg.v22.i44.9765

114.    Herman A, Tambor K, Herman A. Linalool Affects the Antimicrobial Efficacy of Essential Oils. Curr Microbiol. 2016;72(2):165-172. doi:10.1007/s00284-015-0933-4

115.    Scientific Opinion on the safety and efficacy of aliphatic, alicyclic and aromatic saturated and unsaturated tertiary alcohols and esters with esters containing tertiary alcohols ethers (chemical group 6) when used as flavourings for all animal species. EFSA J. 2012;10(11):2966. doi:10.2903/j.efsa.2012.2966

116.    Rombolà L, Amantea D, Russo R, et al. Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain. Mini Rev Med Chem. 2016;16(9):721-728. http://www.ncbi.nlm.nih.gov/pubmed/26996621. Accessed December 26, 2018.

117.    Koulivand PH, Khaleghi Ghadiri M, Gorji A. Lavender and the nervous system. Evid Based Complement Alternat Med. 2013;2013:681304. doi:10.1155/2013/681304

118.    National Center for Biotechnology Information. Malic Acid. PubChem Compound Database.

119.    Abraham GE, Flechas JD. Management of Fibromyalgia: Rationale for the Use of Magnesium and Malic Acid. J Nutr Med. 1992;3(1):49-59. doi:10.3109/13590849208997961

120.    Tyka AK, Chwastowski M, Cison T, et al. Effect of creatine malate supplementation on physical performance, body composition and selected hormone levels in spinters and long-distance runners. Acta Physiol Hung. 2015;102(1):114-122. doi:10.1556/APhysiol.102.2015.1.12

121.    Rodgers AL, Webber D, de Charmoy R, Jackson GE, Ravenscroft N. Malic Acid Supplementation Increases Urinary Citrate Excretion and Urinary pH: Implications for the Potential Treatment of Calcium Oxalate Stone Disease. J Endourol. 2014;28(2):229-236. doi:10.1089/end.2013.0477

122.    National Center for Biotechnology Information. Methyl Anthranilate. PubChem Database.

123.    Askham LR. Proceedings – Vertebrate Pest Conference. In: Proceedings… Vertebrate Pest Conference (USA). University of California, Davis; 1992. http://agris.fao.org/agris-search/search.do?recordID=US9416552. Accessed December 26, 2018.

124.    Cummings JL, Avery ML, Pochop PA, et al. Evaluation of a methyl anthranilate formulation for reducing bird damage to blueberries. Crop Prot. 1995;14(3):257-259. doi:10.1016/0261-2194(95)00016-F

125.    Aquilina G, Bories G, Chesson A, et al. Scientific Opinion on the safety and efficacy of anthranilate derivatives (chemical group 27) when used as flavourings for all animal species 1 EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) Anthranilate derivatives (CG 27) for all species. EFSA J. 2011;9(12):2441. doi:10.2903/j.efsa.2011.2441

126.    Rao VRS, Raju SS, Sarma VU, et al. Simultaneous determination of bioactive compounds in Piper nigrum L. and a species comparison study using HPLC-PDA. Nat Prod Res. 2011;25(13):1288-1294. doi:10.1080/14786419.2010.535158

127.    Li X, Choi Y, Yanakawa Y, Park T. Piperonal prevents high-fat diet-induced hepatic steatosis and insulin resistance in mice via activation of adiponectin/AMPK pathway. Int J Obes. 2014;38(1):140-147. doi:10.1038/ijo.2013.70

128.    Chu S, Narayan VP, Sung M-K, Park T. Piperonal attenuates visceral adiposity in mice fed a high-fat diet: potential involvement of the adenylate cyclase-protein kinase A dependent pathway. Mol Nutr Food Res. 2017;61(11):1601124. doi:10.1002/mnfr.201601124

129.    Meriga B, Parim B, Chunduri VR, et al. Antiobesity potential of Piperonal: promising modulation of body composition, lipid profiles and obesogenic marker expression in HFD-induced obese rats. Nutr Metab (Lond). 2017;14(1):72. doi:10.1186/s12986-017-0228-9

130.    Anantharaju PG, Gowda PC, Vimalambike MG, Madhunapantula S V. An overview on the role of dietary phenolics for the treatment of cancers. Nutr J. 2016;15(1):99. doi:10.1186/s12937-016-0217-2

131.    del Olmo A, Calzada J, Nuñez M. Benzoic acid and its derivatives as naturally occurring compounds in foods and as additives: Uses, exposure, and controversy. Crit Rev Food Sci Nutr. 2017;57(14):3084-3103. doi:10.1080/10408398.2015.1087964

132.    Aguilar F, Crebelli R, Domenico A Di, et al. Scientific Opinion on the re-evaluation of benzoic acid (E 210), sodium benzoate (E 211), potassium benzoate (E 212) and calcium benzoate (E 213) as food additives; Scientific Opinion on the re-evaluation of benzoic acid (E 210), sodium benzoate (E 211), potassium benzoate (E 212) and calcium benzoate (E 213) as food additives. EFSA J. 2016;14(3):110. doi:10.2903/j.efsa.2016.4433

133.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1021. Accessed December 26, 2018.

134.    Qualley A V., Widhalm JR, Adebesin F, Kish CM, Dudareva N. Completion of the core  -oxidative pathway of benzoic acid biosynthesis in plants. Proc Natl Acad Sci. 2012;109(40):16383-16388. doi:10.1073/pnas.1211001109

135.    Andersen FA. Final report on the safety assessment of Benzyl Alcohol, Benzoic Acid, and Sodium Benzoate. In:International Journal of Toxicology. Vol 20. ; 2001:23-50. doi:10.1080/10915810152630729

136.    Food Standards Authority Australia New Zealand (FSANZ). SCHEDULE 1 Permitted Uses of Food Additives by Food Type. http://www.foodstandards.gov.au/code/Documents/standard_1_3_1_additives_vol_2_v1321.pdf. Accessed December 27, 2018.

137.    Fidler MC, Davidsson L, Zeder C, Hurrell RF. Erythorbic acid is a potent enhancer of nonheme-iron absorption.Am J Clin Nutr. 2004;79(1):99-102. doi:10.1093/ajcn/79.1.99

138.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3041. Accessed December 27, 2018.

139.    Aguilar F, Crebelli R, Domenico A Di, et al. Scientific Opinion on the re-evaluation of erythorbic acid (E 315) and sodium erythorbate (E 316) as food additives; Scientific Opinion on the re-evaluation of erythorbic acid (E 315) and sodium erythorbate (E 316) as food additives. EFSA J. 2016;14(1):4360-4362. doi:10.2903/j.efsa.2016.4360

140.    Miura K, Yazama F, Tai A. Oxidative stress-mediated antitumor activity of erythorbic acid in high doses. Biochem Biophys Reports. 2015;3:117-122. doi:10.1016/j.bbrep.2015.07.018

141.    Scientific Opinion on the safety evaluation of the substance, thiodipropionic acid, ditetradecyl ester, CAS No. 16545-54-3, for use in food contact materials. EFSA J. 2011;9(4):2126. doi:10.2903/j.efsa.2011.2126

142.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3109. Accessed December 27, 2018.

143.    Hocman G. Chemoprevention of cancer: phenolic antioxidants (BHT, BHA). Int J Biochem. 1988;20(7):639-651. http://www.ncbi.nlm.nih.gov/pubmed/3053283. Accessed December 27, 2018.

144.    Laflamme D, Izquierdo O, Eirmann L, Binder S. Myths and Misperceptions About Ingredients Used in Commercial Pet Foods. Vet Clin North Am Small Anim Pract. 2014;44(4):689-698. doi:10.1016/j.cvsm.2014.03.002

145.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=182.3169. Accessed December 27, 2018.

146.    Rychen G, Aquilina G, Azimonti G, et al. Safety and efficacy of butylated hydroxyanisole (BHA) as a feed additive for all animal species. EFSA J. 2018;16(3). doi:10.2903/j.efsa.2018.5215

147.    Iverson F. Phenolic antioxidants: Health protection branch studies on butylated hydroxyanisole. Cancer Lett. 1995;93(1):49-54. doi:10.1016/0304-3835(95)03787-W

148.    Kahl R, Kappus H. [Toxicology of the synthetic antioxidants BHA and BHT in comparison with the natural antioxidant vitamin E]. Z Lebensm Unters Forsch. 1993;196(4):329-338. http://www.ncbi.nlm.nih.gov/pubmed/8493816. Accessed December 27, 2018.

149.    Williams GM, Iatropoulos MJ, Whysner J. Safety assessment of butylated hydroxyanisole and butylated hydroxytoluene as antioxidant food additives. Food Chem Toxicol. 37(9-10):1027-1038. http://www.ncbi.nlm.nih.gov/pubmed/10541460. Accessed December 27, 2018.

150.    Hirose M, Yada H, Hakoi K, Takahashi S, Ito N. Modification of carcinogenesis by alpha-tocopherol, t-butylhydroquinone, propyl gallate and butylated hydroxytoluene in a rat multi-organ carcinogenesis model. Carcinogenesis. 1993;14(11):2359-2364. http://www.ncbi.nlm.nih.gov/pubmed/8242867. Accessed December 27, 2018.

151.    Aguilar R, Crebelli B, Dusemund P, et al. EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS); Scientific Opinion on the re-evaluation of Butylated hydroxytoluene BHT (E 321) as a food additive Scientific Opinion on the re-evaluation of butylated hydroxytoluene BHT (E 321) as a . EFSA J. 2012;10(3):2588-2590. doi:10.2903/j.efsa.2012.2588

152.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3225. Accessed December 27, 2018.

153.    Dzanis DA. Safety of Ethoxyquin in Dog Foods. J Nutr. 1991;121(suppl_11):S163-S164. doi:10.1093/jn/121.suppl_11.S163

154.    CABEL MC, WALDROUP PW, SHERMER WD, CALABOTTA DF. Effects of Ethoxyquin Feed Preservative and Peroxide Level on Broiler Performance. Poult Sci. 1988;67(12):1725-1730. doi:10.3382/ps.0671725

155.    Zhu J, Carozzi VA, Reed N, et al. Ethoxyquin provides neuroprotection against cisplatin-induced neurotoxicity. Sci Rep. 2016;6(1):28861. doi:10.1038/srep28861

156.    Safety and efficacy of ethoxyquin (6?ethoxy?1,2?dihydro?2,2,4?trimethylquinoline) for all animal species. EFSA J. 2015;13(11). doi:10.2903/j.efsa.2015.4272

157.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=573.380. Accessed December 27, 2018.

158.    Zhu J, Chen W, Mi R, Zhou C, Reed N, Höke A. Ethoxyquin prevents chemotherapy-induced neurotoxicity via Hsp90 modulation. Ann Neurol. 2013;74(6):893-904. doi:10.1002/ana.24004

159.    B?aszczyk A, Augustyniak A, Skolimowski J. Ethoxyquin: An Antioxidant Used in Animal Feed. Int J Food Sci. 2013;2013:1-12. doi:10.1155/2013/585931

160.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3280&SearchTerm=dilauryl thiodipropionate. Accessed December 27, 2018.

161.    Sasseville D, Alfalah M, Lacroix J-P. “Parabenoia” Debunked, or “Who’s Afraid of Parabens?”. Dermatitis. 2015;26(6):254-259. doi:10.1097/DER.0000000000000147

162.    Soni MG, Taylor SL, Greenberg NA, Burdock GA. Evaluation of the health aspects of methyl paraben: a review of the published literature. Food Chem Toxicol. 2002;40(10):1335-1373. http://www.ncbi.nlm.nih.gov/pubmed/12387298. Accessed December 27, 2018.

163.    Opinion of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a Request from the Commission Related to Para Hydroxybenzoates The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials In.; 2004. http://www.efsa.europa.eu/sites/default/files/scientific_output/files/main_documents/83.pdf. Accessed December 27, 2018.

164.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1670. Accessed December 27, 2018.

165.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1490&SearchTerm=methylparaben . Accessed December 27, 2018.

166.    Scientific Opinion on the re?evaluation of sulfur dioxide (E 220), sodium sulfite (E 221), sodium bisulfite (E 222), sodium metabisulfite (E 223), potassium metabisulfite (E 224), calcium sulfite (E 226), calcium bisulfite (E 227) and potassium bisulfite (E 228) as food additives. EFSA J. 2016;14(4). doi:10.2903/j.efsa.2016.4438

167.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3637. Accessed December 27, 2018.

168.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3616. Accessed December 27, 2018.

169.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3766. Accessed December 27, 2018.

170.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3798. Accessed December 27, 2018.

171.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3739. Accessed December 27, 2018.

172.    Beckman Sundh U, Binderup M-L, Bolognesi C, et al. Scientific Opinion on the safety evaluation… CEF); Sci EFSA J. 2013;11(4):3155. doi:10.2903/j.efsa.2013.3155

173.    Zar T, Graeber C, Perazella MA. Reviews: Recognition, Treatment, and Prevention of Propylene Glycol Toxicity. Semin Dial. 2007;20(3):217-219. doi:10.1111/j.1525-139X.2007.00280.x

174.    Tobe M, Furuya T, Kawasaki Y, et al. Six-month toxicity study of butylated hydroxyanisole in beagle dogs. Food Chem Toxicol. 24(10-11):1223-1228. http://www.ncbi.nlm.nih.gov/pubmed/3804124. Accessed December 27, 2018.

175.    Weil CS, Woodside MD, Smyth HF, Carpenter CP. Results of feeding propylene glycol in the diet to dogs for two years. Food Cosmet Toxicol. 1971;9(4):479-490. doi:10.1016/0015-6264(71)90078-2

176.    Agency for Toxic Substances and Disease Registry, Public Health Service USD of H and HS. TOXICOLOGICAL PROFILE FOR PROPYLENE GLYCOL. Atlanta, GA; 1997. https://www.atsdr.cdc.gov/toxprofiles/tp189.pdf. Accessed December 27, 2018.

177.    Staples CA, Davis JW. An examination of the physical properties, fate, ecotoxicity and potential environmental risks for a series of propylene glycol ethers. Chemosphere. 2002;49(1):61-73. http://www.ncbi.nlm.nih.gov/pubmed/12243331. Accessed December 27, 2018.

178.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=184.1666. Accessed December 27, 2018.

179.    Bigner DR, Goff JP, Faust MA, Tyler HD, Horst RL. Comparison of Oral Sodium Compounds for the Correction of Acidosis. J Dairy Sci. 1997;80(9):2162-2166. doi:10.3168/jds.S0022-0302(97)76163-0

180.    SCHULTZ LH. Treatment of ketosis in dairy cattle with sodium propionate. Cornell Vet. 1952;42(1):148-155. http://www.ncbi.nlm.nih.gov/pubmed/14905895. Accessed December 27, 2018.

181.    Kishimoto Y, Wakabayashi S, Takeda H. Effects of intravenous injection and intraperitoneal continual administration of sodium propionate on serum cholesterol levels in rats. J Nutr Sci Vitaminol (Tokyo). 1995;41(1):73-81. http://www.ncbi.nlm.nih.gov/pubmed/7616328. Accessed December 27, 2018.

182.    Wang J, Wei Z, Zhang X, Wang Y, Yang Z, Fu Y. Propionate Protects against Lipopolysaccharide-Induced Mastitis in Mice by Restoring Blood–Milk Barrier Disruption and Suppressing Inflammatory Response. Front Immunol. 2017;8. doi:10.3389/fimmu.2017.01108

183.    Chambers ES, Byrne CS, Aspey K, et al. Acute oral sodium propionate supplementation raises resting energy expenditure and lipid oxidation in fasted humans. Diabetes, Obes Metab. 2018;20(4):1034-1039. doi:10.1111/dom.13159

184.    Safari R, Hoseinifar SH, Kavandi M. Modulation of antioxidant defense and immune response in zebra fish (Danio rerio) using dietary sodium propionate. Fish Physiol Biochem. 2016;42(6):1733-1739. doi:10.1007/s10695-016-0253-z

185.    Safety of the extension of use of sodium propionate (E 281) as a food additive. EFSA J. 2016;14(8). doi:10.2903/j.efsa.2016.4546

186.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1784. Accessed December 27, 2018.

187.    Silva De Souza SM, Hirata R, Moreira LO, et al. Influence of stannous chloride on the adhesive properties of Corynebacterium diphtheriae strains. Int J Mol Med. 2003;12(4):657-661. http://www.ncbi.nlm.nih.gov/pubmed/12964050. Accessed December 27, 2018.

188.    João-Souza SH, Bezerra SJC, de Freitas PM, et al. In situ evaluation of fluoride-, stannous- and polyphosphate-containing solutions against enamel erosion. J Dent. 2017;63:30-35. doi:10.1016/j.jdent.2017.05.014

189.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=184.1845. Accessed December 27, 2018.

190.    Younes M, Aggett P, Aguilar F, et al. Re?evaluation of stannous chloride (E 512) as food additive. EFSA J. 2018;16(6). doi:10.2903/j.efsa.2018.5295

191.    Wang X-B, Cui H, Liu X, Du J-B. Sulfur dioxide: foe or friend for life? Histol Histopathol. 2017;32(12):1231-1238. doi:10.14670/HH-11-904

192.    Oehha. Sulfur Dioxide in Dried Fruit, Interpretive Guidelines.; 2012. http://www.oehha.ca.gov/prop65/prop65_list/Newlist.html. Accessed December 27, 2018.

193.    Freedman BJ. Sulphur dioxide in foods and beverages: its use as a preservative and its effect on asthma. Br J Dis Chest. 1980;74(2):128-134. http://www.ncbi.nlm.nih.gov/pubmed/7426352. Accessed December 27, 2018.

194.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=182.3862. Accessed December 27, 2018.

195.    Chen S, Zheng S, Liu Z, et al. Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats. Lab Investig. 2015;95(2):142-156. doi:10.1038/labinvest.2014.147

196.    Wang L-F, Su S-W, Wang L, et al. Tert-butylhydroquinone ameliorates doxorubicin-induced cardiotoxicity by activating Nrf2 and inducing the expression of its target genes. Am J Transl Res. 2015;7(10):1724-1735. http://www.ncbi.nlm.nih.gov/pubmed/26692920. Accessed December 27, 2018.

197.    Zeng X-P, Li X-J, Zhang Q-Y, et al. Tert-Butylhydroquinone Protects Liver Against Ischemia/Reperfusion Injury in Rats Through Nrf2-Activating Anti-Oxidative Activity. Transplant Proc. 2017;49(2):366-372. doi:10.1016/j.transproceed.2016.12.008

198.    Zhou N-Q, Liu N, Li P, Ping S, Peng Q-S, Shi W-D. Tert-butylhydroquinone promotes angiogenesis and improves heart functions in rats after myocardial infarction. Clin Exp Hypertens. 2017;39(5):402-408. doi:10.1080/10641963.2016.1259322

199.    Gharavi N, Haggarty S, El-Kadi AOS. Chemoprotective and carcinogenic effects of tert-butylhydroquinone and its metabolites. Curr Drug Metab. 2007;8(1):1-7. http://www.ncbi.nlm.nih.gov/pubmed/17266519. Accessed December 27, 2018.

200.    van Esch GJ. Toxicology of tert-butylhydroquinone (TBHQ). Food Chem Toxicol. 1986;24(10-11):1063-1065. doi:10.1016/0278-6915(86)90289-9

201.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=172.185. Accessed December 27, 2018.

202.    Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) on a request from the Commission related to tertiary-Butylhydroquinone (TBHQ). EFSA J. 2004;2(10):84. doi:10.2903/j.efsa.2004.84

203.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=74.250. Accessed December 25, 2018.

204.    Food and Drug Administration (FDA). CFR – Code of Federal Regulations Title 21.; 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=74.302. Accessed December 25, 2018.

Posted in Nutrition | 19 Comments

Herbalists try again for medical specialty status.

In 2017 and 2018, I covered extensivelythe efforts of the American College of Veterinary Botanical Medicine (ACVBM) to achieve recognition as a medical specialty by the American Board of Veterinary Specialties (ABVS). I opposed recognition for several reasons:

  1. Prescribing of herbal medicine in the veterinary field is based mostly on folk medicine traditions, especially Traditional Chinese Veterinary Medicine (TCVM), which are mostly unproven and often deeply inconsistent with scientific medicine.

  2. Most herbalists, including leaders of the ACVBM, promote many alternative therapies other than herbal medicine, and these people often have medical philosophies inconsistent with science and science-based medicine.
  • Very few herbal remedies have been properly tested scientifically, so there is an insufficient foundation of knowledge to justify a specialty. What scientific work has been done in this area falls naturally under the domain of existing specialty organizations, such as the American College of Veterinary Clinical Pharmacology (ACVCP), so there is no need to create a new college.
  • Herbalism is not a recognized medical specialty in human or veterinary medicine in Europe, Australia, or the United States because it has not yet developed a legitimate scientific basis, and recognition of the ACVBM would give a misleading appearance of scientific legitimacy to a set of approaches reliant predominantly on folk traditions.

The ABVS tabled the ACVBM petitionand recommended the group seek subspecialty status under the ACVCP. The ABVS process is quite secretive, so little has been made public about it, but it appears that ACVCP wished to set up a methodical and careful process to consider any potential relationship between the groups, and the ACVBM decided it did not wish to pursue this process. Instead, the ACVBM has reactivated the tabled application for standalone recognition from ABVS. The latest version of the ACVBM petitiondiffers in some respects from the original petition submitted in 2016. The original petition, and subsequent communications with ABVS, tried to emphasize the mainstream, scientific nature of herbal medicine and downplay the alternative nature of the practice. The current petition does this as well, but it seems to emphasize more strongly the differences between a science-based approach to medicine and the philosophy of herbalism derived from traditional sources.

Here are a few examples:

Botanical medicine looks at pharmacognosy, not from the perspective of single molecule phytochemical discovery for the development of new drug leads, but rather to validate or understand traditional medicine and how the herbs work….That the whole plant is more therapeutic than a constituent is a fundamental principle of botanical medicine supported by research.

Principles of botanical medicine respect tradition as a source of empirical evidence that informs formal research design. The study of traditional use of plants within a culture is termed ethnobotany, and the study of traditional medicines is known as ethnomedicine, or ethnoveterinary medicine. Research may validate traditional uses.

Research may validate traditional use, or it may not (which is more common but not acknowledged in the petition). This statement clearly shows the unscientific view that the goal of research is to “validate or understand” the beliefs of traditional folk medicine, rather than to test them and find out if they are true or not. It also accepts as a central principle the traditional notion that whole plants are more effective than isolated plant compounds, though there is virtually no real-world research evidence supporting this idea.

The ACVBM differentiates themselves by interest in the rich knowledge base of traditional botanical medicine use and ethnobotany combined with modern scientific, chemical, toxicological, pharmacological clinical application and research in a practice that could be appropriately termed rationale phytotherapy to distinguish from colleagues who may only embrace traditional findings or who may eschew scientific findings…

This is encouraging, though given the background and other practices of the organizing committee for the ACVBM, I am not convince that the organization is likely to ever give priority to science over traditional knowledge if the two conflict. TCVM vets and practitioners of homeopathy and not really the most reliable guardians of science-based practice.

Veterinarians using botanical medicine have a patient centered approach, whereby the botanical medicines are selected based on the individual signs and pathophysiology as well as the diagnosis. So that two dogs with diabetes for example, may be treated with two different sets of botanical medicines. 

This is the common claim of alternative medicine to “individualize” therapy to a greater extent than scientific medicine. I’ve written many times beforeabout why this is a misleading and empty claim that hides the fact that such supposedly “individualized” therapies are almost never scientifically tested or shown to be effective or superior in any way to science-based practices.

The ACVBM also holds the philosophical position, common in alternative medicine, that tradition and personal or anecdotal experience are reliable and sufficient evidence and may even be superior to controlled scientific research. Here are some illustrations:

Sources of information include:

Traditional use. The bewildering variety of ethnoveterinary practices, ethnobotanical uses and folk practices around the world coupled with confounding aspects of cultural, placebo and other non-specific effects make reliable conclusions from any one tradition difficult. Frequently however, traditional use informs research and pharmacological activity is often found to be closely correlated. There are recurring themes in traditional medicine and persistent therapeutic approaches consistent with the use of “archetypal” chemical groups within plants.

I certainly agree that traditional use is inconsistent, low-quality evidence that has rarely led to definitive success in treatment. I disagree, however, with the claim that scientific evidence frequently confirms traditional use. Folk herbalism often uses plants for a wide variety of unrelated problems, and when properly tested the rare few uses which seem to have some real benefits are celebrated and the many that were useless are forgotten.

Collective clinical experience over decades. There is also the clinical experience of veterinary practitioners to consider- thousands of educated veterinary practitioners worldwide prescribe herbal medicines in their work. This has advantages of being in a modern veterinary context. Veterinary practitioners of botanical medicine have written texts and taught other veterinarians to achieve repeatable results within the botanical framework.

Collective clinical experience is another way of saying “anecdote,” and as the saying goes, the plural of “anecdote” is not “data.” The fact that people are “experts” in herbal medicine and have written and taught about it doesn’t, in itself, show that the beliefs and practices being passed along are correct or useful.

The third data source is substantial and scientifically sound but maybe not as clinically relevant to veterinary botanical medicine. The available published literature on phytochemistry and preclinical pharmacology…[this does] not however provide confirmation of a clinical effect; experience in practice is that the effect of the whole plant is rarely predicated on the effects of its parts….it is appreciated that herbs have been dismissed by many in the profession as the refuge of the uncritical. However, when all the sources of information come together and are integrated with pharmacological insights, something important happens; unique treatment strategies for treating notoriously difficult clinical problems become possible and the desire of the ACVBM is for animals to benefit from the efforts of this group to further develop the field. To be a fully effective therapy, it is not enough simply to know about the herbs themselves. Information must also be sought about how and when to use these herbs in response to various therapeutic challenges. Therapeutic approaches are different from those that underpin conventional medicine.

Again, this is a position that says scientific study, including pharmacological analysis of the compound sin plant remedies, is useful, but only as a supplement to the wisdom of tradition and personal experience, which still maintains without much evidence that traditional whole-plant remedies work better than plant-derived medicines. This is a pretty direct refutation of the principles of pharmacognosy (development of medicines from plants), which I suspect is a response to the rejection of the ACVBM by the ACVCP.

The universal role of plants in the treatment of disease is exemplified by their use in all the major systems of traditional medicine and ethnomedicine irrespective of their underlying philosophical premise.

So because lots of people have done it, this means it is worth doing? Not a rational perspective.

The practitioner of botanical medicine regards the whole formula or whole extract as the “active ” component” in the therapeutic context.

The concept of polyvalent or multifaceted activity of the medicine is central to botanical medicine – in the context of the advantage of chemical complexity -and even a single herbal extract is a natural multi agent medicine that can simultaneously target a range of desirable pharmacological effects.

The veterinary botanical practitioner prefers not just to prescribe chemically complex herbs, but often administers them in complex formulations, compared to conventional medicine preferring to prescribe a single drug. The practitioner chooses herbs or formulas for a cooperative or facilitating effect between the components to address therapeutic goals.

Again, these are tenets of faith, not scientifically proven propositions.

Philosophically the veterinary botanical medicine practitioner practices conventional medicine but overlays that practice with the use of botanical medicines in a framework of botanical principles to expand their options for treatment of disease and optimizing health.

Practitioners appreciate traditional knowledge as just one potential source of information, when coupled with published research and clinical experience, herbs can be prescribed safely and effectively.

This is the principle of “integrative medicine,” which holds that mixing the scientific with the unscientific and the proven with the unproven somehow makes the whole treatment approach better. As infectious disease doc Marc Crislip has put it, “If you integrate fantasy with reality, you do not instantiate reality. If you mix cow pie with apple pie, it does not make the cow pie taste better; it makes the apple pie worse.”

The ACVBM petition goes on to acknowledge that many veterinarians are concerned about the paucity of scientific research evidence concerning herbal medicine (though not to acknowledge directly that this is a well-founded concern). However, it then employs the tu quoquefallacy, arguing that since veterinary medicine as a whole suffers from a deficiency of high-quality research evidence, this should not be a barrier to treating herbal medicine as a legitimate scientific specialty. This misses the point, which is that we should be seeking more and better evidence, not giving up on the centrality of scientific research evidence to good medical practice. Giving the specialty imprimatur to an especially evidence-poor alternative practice only weakens the overall scientific basis of veterinary medicine.

An important basis of herbal medicine is the pharmacology and mechanisms of actions of plants and plant extracts, however they differ from drugs in their complexity, and in the underlying ethnomedical knowledge base used to initiate study of them. The botanical medicine diplomate can provide context to client and referring veterinarian inquiries, from both the ethnomedical and pharmacologic perspectives.

This basically suggests that the main reason herbalists should be considered specialists is that they can add the value of traditional knowledge to the scientific perspective on plant compounds. Again, this only makes sense if you presume, generally wrongly, that such traditional knowledge is useful or accurate much of the time.

Bottom Line

Nothing appears to have fundamentally changed in the ACVBM approach since I began to examine it in 2017. The ACVBM is a bit more direct in the latest petition in their claims that the primary reason they should be a distinct specialty group is because of their greater familiarity with traditional sources of knowledge about plant medicines. While they may acknowledge some need for scientific research into herbal remedies, they consistently claim that conventional veterinarians cannot effectively conduct such research without being familiar with the folk medicine approach to herbalism. 

This implies that scientists cannot test the effectiveness of any medical therapy without being experts in prescientific folk beliefs about it. Can we not evaluate surgery without being experts in bloodletting? Is the study of antibiotics to treat syphilis futile unless we have first-hand training in the use of the poison mercury for treating this disease? 

Ultimately, the ACVBM petition is simply another of the many efforts of alternative medicine to create an exception to the normal, scientific standards of evidence currently applied to medical practices. If scientific research works better than tradition or personal experience to determine which therapies are effective and why (and the evidence it does is overwhelming), then there is no need to give experts in folk medicine beliefs special status as experts in a discipline that can be readily and effectively studied with current scientific methods. 

I believe there is great potential for effective medical therapies in plant chemistry, and we have already realized this in many modern drugs. I also believe folk tradition has only very rarely stumbled across truly effective treatments through trial-and-error and anecdote, and it is not a particularly useful guide to which plants we should study for which problems. Those herbalists truly committed to a scientific medical practice should work within the accepted standards of scientific evidence to validate (or invalidate) specific herbal practices, rather than trying to create a group that will exist primarily to promote and self-validate their own alternative standards of evidence.

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Don’t Give Raw Milk to Your Pets!

A reader recently sent me a link to this little advertisement. 

This is an illustration of a popular bit of alternative nonsense, the idea that raw milk has magical health-giving properties. The idea owes a lot to the Appeal to Nature Fallacy, the idea that something “natural” is inherently. Safer and healthier than something “artificial.” Of course, those words have little real meaning since the distinction is arbitrary and unreliable. And in any case, the effects of such “natural” substances as Salmonella, Ebola, Uranium, asbestos, and many others make it pretty obvious that natural does not mean safe or health.

Like so many proponents of irrational nutritional ideas, raw milk promoters exaggerate, ignore, and misuse science to create the illusion that there is real evidence behind their claims. They also make free use of anecdotes which, as I have discussed many times, prove absolutely nothing.  The reality is that there is no reliable evidence that raw milk, from goats or any other species, has health benefits that can’t be obtained much more safely from pasteurized milk (that is, milk that has been heated to kill bacteria, parasites, and other dangerous microorganisms). 

If you feed your dog or cat raw milk, you are taking a serious risk of illness for your pet and yourself without any reasonable evidence to suggest a benefit that would make that risk worth taking. Just as raw diets in general have clearly established dangers and no proven benefits, so raw milk is a. poor bet with serious risks.  That is why raw milk products are generally illegalfor human consumption under federal and state law.

Here are some useful facts and resources to give you the real truth about the dangers of raw milk.

The CDC page on raw milk provides consumers with fact-based advice on the dangers and purported benefits of raw milk.

This organization collects information about raw milk and stories of families harmed by misguided belief in claims about raw milk.

Basnet S, Schneider M, Gazit A, Mander G, Doctor A. Fresh Goat’s Milk for Infants: Myths and Realities–A Review.Pediatrics. 2010;125(4):e973-e977. doi:10.1542/peds.2009-1906

Many infants are exclusively fed unmodified goat’s milk as a result of cultural beliefs as well as exposure to false online information. Anecdotal reports have described a host of morbidities associated with that practice, including severe electrolyte abnormalities, metabolic acidosis, megaloblastic anemia, allergic reactions including life-threatening anaphylactic shock, hemolytic uremic syndrome, and infections. We describe here an infant who was fed raw goat’s milk and sustained intracranial infarctions in the setting of severe azotemia and hypernatremia, and we provide a comprehensive review of the consequences associated with this dangerous practice.

Oliver SP, Boor KJ, Murphy SC, Murinda SE. Food Safety Hazards Associated with Consumption of Raw Milk.Foodborne Pathog Dis. 2009;6(7):793-806. doi:10.1089/fpd.2009.0302

An increasing number of people are consuming raw unpasteurized milk. Enhanced nutritional qualities, taste, and health benefits have all been advocated as reasons for increased interest in raw milk consumption. However, science-based data to substantiate these claims are limited. People continue to consume raw milk even though numerous epidemiological studies have shown clearly that rawmilk can be contaminated by a variety of pathogens, some of which are associated with human illness and disease. Several documented milkborne disease outbreaks occurred from 2000-2008 and were traced back to consumption of raw unpasteurized milk. Numerous people were found to have infections, some were hospitalized, and a few died. In the majority of these outbreaks, the organism associated with the milkborne outbreak was isolated from the implicated product(s) or from subsequent products made at the suspected dairy or source. In contrast, fewer milkborne disease outbreaks were associated with consumption of pasteurized milk during this same time period. Twenty nine states allow the sale of raw milk by some means. Direct purchase, cow-share or leasing programs, and the sale of raw milk as pet food have been used as means for consumers to obtain raw milk. Where raw milk is offered for sale, strategies to reduce risks associated with raw milk and products made from raw milk are needed. Developing uniform regulations including microbial standards for raw milk to be sold for human consumption, labeling of raw milk, improving sanitation during milking, and enhancing and targeting educational efforts are potential approaches to this issue. Development of pre- and postharvest control measures to effectively reduce contamination is critical to the control of pathogens in raw milk. One sure way to prevent raw milk-associated foodborne illness is for consumers to refrain from drinking raw milk and from consuming dairy products manufactured using raw milk.

Committee on Infectious Diseases, Committee on Nutrition, American Academy of Pediatrics. Consumption of Raw or Unpasteurized Milk and Milk Products by Pregnant Women and Children.Pediatrics. 2014;133(1):175-179. doi:10.1542/peds.2013-3502

Sales of raw or unpasteurized milk and milk products are still legal in at least 30 states in the United States. Raw milk and milk products from cows, goats, and sheep continue to be a source of bacterial infections attributable to a number of virulent pathogens, including Listeria monocytogenes, Campylobacter jejuni, Salmonella species, Brucella species, and Escherichia coli O157. These infections can occur in both healthy and immunocompromised individuals, including older adults, infants, young children, and pregnant women and their unborn fetuses, in whom life-threatening infections and fetal miscarriage can occur. Efforts to limit the sale of raw milk products have met with opposition from those who are proponents of the purported health benefits of consuming raw milk products, which contain natural or unprocessed factors not inactivated by pasteurization. However, the benefits of these natural factors have not been clearly demonstrated in evidence-based studies and, therefore, do not outweigh the risks of raw milk consumption. Substantial data suggest that pasteurized milk confers equivalent health benefits compared with raw milk, without the additional risk of bacterial infections. The purpose of this policy statement was to review the risks of raw milk consumption in the United States and to provide evidence of the risks of infectious complications associated with consumption of unpasteurized milk and milk products, especially among pregnant women, infants, and children.

LeJeune JT, Rajala?Schultz PJ, Rajala-Schultz PJ. Unpasteurized Milk: A Continued Public Health Threat.Clin Infect Dis. 2009;48(1):93-100. doi:10.1086/595007

Although milk and dairy products are important components of a healthy diet, if consumed unpasteurized, they also can present a health hazard due to possible contamination with pathogenic bacteria. These bacteria can originate even from clinically healthy animals from which milk is derived or from environmental contamination occurring during collection and storage of milk. The decreased frequency of bovine carriage of certain zoonotic pathogens and improved milking hygiene have contributed considerably to decreased contamination of milk but have not, and cannot, fully eliminate the risk of milkborne disease. Pasteurization is the most effective method of enhancing the microbiological safety of milk. The consumption of milk that is not pasteurized increases the risk of contracting disease from a foodstuff that is otherwise very nutritious and healthy. Despite concerns to the contrary, pasteurization does not change the nutritional value of milk. Understanding the science behind this controversial and highly debated topic will provide public health care workers the information needed to discern fact from fiction and will provide a tool to enhance communication with clients in an effort to reduce the incidence of infections associated with the consumption of unpasteurized milk and dairy products.

Langer AJ, Ayers T, Grass J, Lynch M, Angulo FJ, Mahon BE. Nonpasteurized dairy products, disease outbreaks, and state laws-United States, 1993-2006Emerg Infect Dis. 2012;18(3):385-391. doi:10.3201/eid1803.111370

Although pasteurization eliminates pathogens and consumption of nonpasteurized dairy products is uncommon, dairy-associated disease outbreaks continue to occur. To determine the association of outbreaks caused by nonpasteurized dairy products with state laws regarding sale of these products, we reviewed dairy-associated outbreaks during 1993-2006. We found 121 outbreaks for which the product’s pasteurization status was known; among these, 73 (60%) involved nonpasteurized products and resulted in 1,571 cases, 202 hospitalizations, and 2 deaths. A total of 55 (75%) outbreaks occurred in 21 states that permitted sale of nonpasteurized products; incidence of nonpasteurized product-associated outbreaks was higher in these states. Nonpasteurized products caused a disproportionate number (?150× greater/unit of product consumed) of outbreaks and outbreak-associated illnesses and also disproportionately affected persons <20 years of age. States that restricted sale of nonpasteurized products had fewer outbreaks and illnesses; stronger restrictions and enforcement should be considered.

Lucey JA. Raw Milk Consumption: Risks and Benefits.Nutr Today. 2015;50(4):189-193. doi:10.1097/NT.0000000000000108

There continues to be considerable public debate on the possible benefits regarding the growing popularity of the consumption of rawmilk. However, there are significant concerns by regulatory, or public health, organizations like the Food and Drug Administration and the Centers for Disease Control and Prevention because of risk of contracting milkborne illnesses if the raw milk is contaminated with human pathogens. This review describes why pasteurization of milk was introduced more than 100 years ago, how pasteurization helped to reduce the incidence of illnesses associated with raw milk consumption, and the prevalence of pathogens in raw milk. In some studies, up to a third of all raw milk samples contained pathogens, even when sourced from clinically healthy animals or from milk that appeared to be of good quality. This review critically evaluates some of the popularly suggested benefits of raw milk. Claims related to improved nutrition, prevention of lactose intolerance, or provision of “good” bacteria from the consumption of raw milk have no scientific basis and are myths. There are some epidemiological data that indicate that children growing up in a farming environment are associated with a decreased risk of allergy and asthma; a variety of environmental factors may be involved and there is no direct evidence that raw milk consumption is involved in any “protective” effect.

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SkeptVet Visits The Pet Doctor Podcast- Are we seeing more cancer in pets?

In October, I wrote a column for Veterinary Practice News (VPN) on the question of whether or not cancer is more common in dogs and cats now than it used to be. This is a core argument in the Truth About Pet Cancer propaganda video series I debunked HERE and HERE. The VPN article caught the attention of Dr. Bernadine Cruz, who asked me to visit her podcast to discuss the subject. Enjoy!

The Pet Doctor Podcast- Are we seeing more cancer in pets.

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Crowdfunding Quackery

One of the most heartbreaking things we all see on social media are appeals for financial help to fund medical treatment. Especially here in the U.S., where healthcare is less readily available to low-income people than in most developed countries, it has become common to see crowdfunding campaigns raising money for medical care. It is inspiring that people are so often willing to help strangers with medical expenses, but it is sad and wrong that patients have to rely on such ad hoc methods for funding the care they need.

As sad as this inherently is, it becomes depressing and infuriating when these crowdfunding campaigns are intended to pay for unproven or quack therapies. Crowdfunding provides a new venue for people to be misled and exploited by proponents of untested, ineffective, and dangerous medical treatments, Now, not only the desperation of patients and their families are taken advantage of, but also compassion of well-meaning strangers who contribute to these campaigns.

Two recent studies have been published in the Journal of the American Medical Association (JAMA) investigating this issue, and these have been publicized through reporting by NPRand other media outlets.

Vox F, Folkers KM, Turi A, Caplan AL. Medical Crowdfunding for Scientifically Unsupported or Potentially Dangerous TreatmentsJAMA. 2018;320(16):1705–1706. doi:10.1001/jama.2018.10264

This study looked at homeopathyand naturopathyfor cancer, hyperbaric oxygen therapy,stem cell treatmentfor brain and spinal cord injury, and long-term antibiotics for Chronic Lyme Disease. All. But the last will be familiar to readers as examples of methods that are dubious or simply don’t work. The study found:

More than 1000 medical crowdfunding campaigns for 5 treatments that are unsupported by evidence or potentially unsafe raised more than $6.7 million… These results reveal that a wide scope of cam- paigns for unsupported, ineffective, or potentially dangerous treatments are moderately successful in obtaining funding. Assuming that the funds raised are spent to pay for these treatments, donors indirectly contributed millions of dollars to practitioners to deliver dubious, possibly unsafe care. 

Snyder J, Turner L, Crooks VA. Crowdfunding for Unproven Stem Cell–Based Interventions. JAMA.2018;319(18):1935–1936. doi:10.1001/jama.2018.3057

The second study focused specifically on stem cell therapies and found similarly large amounts of money committed to campaigns for questionable treatment and also misleading appeals to donors:

Our search identified 408 campaigns seeking donations for stem cell interventions advertised by 50 individual businesses. These campaigns requested $7?439?308 and received pledges for $1?450?011 from 13?050 donors.

Crowdfunding campaigns for unproven stem cell–based interventions underemphasize risks and exaggerate the efficacy of these interventions. These findings suggest that medical crowdfunding campaigns convey potentially misleading messages about stem cell–based interventions. These claims may be especially powerful when embedded within compelling personal narratives. 

As usual, there are no similar studies looking at how much crowdfunding there is for unproven and quack veterinary therapies, but it takes little time and effort to find such campaigns online:

Chi Chi’s Recent Medical Expenses

Chi Chi has an integrated treatment plan that includes both traditional and holistic treatments…Chi Chi takes a number of traditional and Chinese medications to manage her medical conditions… and regular Hyperbaric Oxygen Treatments

Help Give Cayman a Fighting Chance!

extensive therapies including laser, acupuncture

Paralyzed Rescue Dog – Pani

water therapy and laser therapy… cranberry supplements and probiotics…has also been recommended joint supplements

Grace’s Health Treatment?

the best course of treatment for quality of life and longevity is to go a TCM (Traditional Chinese Medicine) route.  With a combination of a fully holistic/organic diet, herbal supplements, chinese medicine and an aggressive 3-day Vitamin drip protocol

Of course, I don’t believe the people making these appeals are doing anything wrong. They desperately want to help the animals they love, and they are willing to ask for help even when that may be difficult for them to do. And those who donate to these campaigns are illustrating the best qualities of the human spirit, compassion and concern for not only friends and family but complete strangers. Most of the appeals I have seen, including those that\ mention alternative therapies, do describe appropriate, science-based medical care, so hopefully these animals are getting the real treatment they need to get well.

Unfortunately, the fact remains that these animal owners and the good Samaritans who help them are paying for treatments that are at best questionable and, in many cases, clearly do not and cannot work. Though the practitioners offering them likely do so believing they are helping, at some point being a healthcare provider should mean knowing better and being required to provide effective treatment. It is hard not to wonder how many pets are harmed by the false belief in these therapies, and how much effective medical care could be paid for with the money that goes to unsupported or quack therapies.

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