There is a lot of mythology out there about food allergies. The recent concern about the potential risks of grain-free diets is only an issue at all because such diets became wildly popular with no evidence that grains were a problem in the first place. A lot of folks blame grains for allergies and other health problems, but there’s no real evidence this is true, and these ingredients probably play a fairly minor role in food allergies in dogs and cats.

Other myths about food allergies include the idea that changing diets can cause them (actually, prolonged exposure is usually needed to develop a sensitivity), that raw foods are less allergenic (nope, only more likely to give you a food-borne illness), and that you can use blood, hair, or saliva tests to diagnose food allergies (sorry, a limited ingredient diet trial is the only way to do this). This last misconception is perpetuated despite evidence from human medicine that it is not true because, quite frankly, it makes people money.

I’ve previously discussed an example of this quackery, Jean Dodds’ Nutriscan allergy testing system. In her book, Dr. Dodds provides many citations to support her claim that this is a legitimate test, but a cursory look at these shows they don’t make that case at all. And there are unpublished reports from at least one allergy specialist that suggest the test is not merely inaccurate but completely useless nonsense:

One veterinary dermatologist has performed her own uncontrolled test of Nutriscan, with Dr. Dodds’ knowledge and permission, and found it entirely unreliable. Twelve samples were submitted for testing in a blind manner, from dogs with known food sensitivities based on dietary testing, dogs with environmental allergies, dogs without allergic disease, and one sample of tap water. All samples including tap water, environmental allergy dogs, and normal dogs showed reactivity to beef, corn, milk and wheat. Some samples showed reactivity to soy. In some cases, these obviously false results would have led to recommendations against diets which actually helped these dogs.

Granted, this is essentially an unpublished anecdote, so while it counters the anecdotes Dodds and others put forward for Nutriscan, it is not published scientific research. Now, however, a different allergy test, using saliva and hair samples to identify allergies, has failed the same test as spectacularly as Nutriscan purportedly did.

Coyner K, Schick A. Hair and saliva test fails to identify allergies in dogs. J Small Anim Pract. October 2018. doi:10.1111/jsap.12952

Our study demonstrates that hair and saliva testing fails not only to identify allergic dermatitis in dogs, but fails to differentiate between animal and non-animal samples, providing essentially identical results, regardless of the origin of the sample.

These authors submitted not only hair and saliva from dogs with known allergies and dogs without allergies, but also fake hair samples from stuffed animals and water (in place of saliva). All of the samples tested positive for some allergies, and there was essentially no difference between the results and random chance.

Bottom Line
Saliva and hair tests for food allergies are a scam and a waste of time and money.

Back in 2011 I wrote about a therapy popular with alternative practitioners called prolotherapy. I try to check in from time to time to see if there is any new evidence for the treatments I consider, and in doing so I did find some new evidence. First, here’s my conclusion from the previous review:

Prolotherapy is a purported treatment for connective tissue and joint pain and disability. It involves injecting substances which induce inflammation and other chemical and cellular reactions into affected tissues. These reactions are theorized to relieve pain and improve function. The logic of this theory is questionable, and no clear mechanism for beneficial effects from prolotherapy has been described, but it is possible that the theory could be valid.

The clinical research on prolotherapy in humans is generally of low quality and results have been mixed. There is great variation in the techniques used by different investigators, so it is difficult to compare or generalize between studies.

There is virtually no controlled research investigating prolotherapy in companion animals, and all claims made for safety and efficacy in these species are based solely on anecdotal evidence.

The use of proltherapy in pets should be viewed as experimental with unknown risks and benefits. Such treatments should be reserved for patients that have significant symptoms that have failed to respond or cannot be treated by conventional means.

What Is It?
Prolotherapy involves injecting substances into joints or musculoskeletal tissue to treat pain and dysfunction. The particular substances used vary. Some are clearly useless (e.g. homeopathic remedies), but the evidence is growing that others may have some beneficial clinical effects. The most common substance currently used is dextrose, a form of sugar, but there are many others, and of course each substance has to be evaluated individually for specific uses.

Does It Work?
The in vitro and lab evidence suggests some potentially useful effects on joint tissues and in lab animals, but of course this level of evidence frequently turns out to be unreliable in predicting the actual effects in patients. At the time of my previous article, most systematic reviews were inconclusive, and the quality of the clinical trial evidence in humans was weak. There is still significant differences of opinions in different reviews, and all call for better quality evidence, but there is an emerging consensus that dextrose prolotherapy may be useful for arthritis in people. Other uses are still not supported by very convincing evidence. Here are some samples of the systematic review literature:

Limited evidence from low-quality studies indicates a beneficial effect of prolotherapy for OA management. The number of participants in these studies was too small to provide reliable evidence…Current data from trials about prolotherapy for OA should be considered preliminary, and future high-quality trials on this topic are warranted.¹

Although anecdotal clinical success guides the use of prolotherapy for many conditions, clinical trial literature supporting evidence-based decision-making for the use of prolotherapy exists for low back pain, several tendinopathies, and osteoarthritis.²

This systematic review suggests that ST and PT may be effective treatment options for AT and that they can be considered safe. Long-term studies and RCTs are still needed to support their recommendation.³

Within the limitations of the study, dextrose prolotherapy may cause significant reduction in mouth opening and pain associated with TMJ hypermobility. Conclusions with regard to reduction of episodes of subluxation/dislocation cannot be drawn. There is a need of more high-quality RCTs with larger sample size and homogenous prolotherapy protocol to draw stronger conclusions on the effect of dextrose prolotherapy in patients with TMJ hypermobility.⁴

Dextrose injections decreased pain in osteoarthritis patients but did not exhibit a positive dose-response relationship following serial injections. Dextrose prolotherapy was found to provide a better therapeutic effect than exercise, local anesthetics, and probably corticosteroids when patients were retested 6 months following the initial injection.⁵

Use of dextrose prolotherapy is supported for treatment of tendinopathies, knee and finger joint OA, and spinal/pelvic pain due to ligament dysfunction. Efficacy in acute pain, as first-line therapy, and in myofascial pain cannot be determined from the literature.⁶

Moderate evidence suggests that prolotherapy is safe and can help achieve significant symptomatic control in individuals with OA. Areas for developing research Future research should focus on larger sample size, standardization of treatment protocol and basic science evidence.⁷

Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.⁸

Systematic review, including meta-analysis, and randomized controlled trials suggest that prolotherapy may be associated with symptom improvement in mild to moderate symptomatic knee osteoarthritis and overuse tendinopathy. Although the mechanism of action is not well understood and is likely multifactorial, a growing body of literature suggests that prolotherapy for knee osteoarthritis may be appropriate for the treatment of symptoms associated with knee osteoarthritis in carefully selected patients who are refractory to conservative therapy and deserves further basic and clinical science investigation for the treatment of osteoarthritis and tendinopathy.⁹

Unfortunately, the same proliferation of research evidence has not happened in veterinary medicine. To date, there is only one study of this treatment in dogs¹⁰ and none in cats.

Sherwood JM, Roush JK, Armbrust LJ, Renberg WC. Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs. J Am Anim Hosp Assoc. 2017;53(3):135-1

This was a small but very high-quality study with appropriate blinding, randomization, control groups, and a mix of subjective and objective outcome measures. That’s the good news. The bad news is there was no significant difference between prolotherapy and placebo in any measure, so the therapy clearly didn’t work. This is only one study, and given the encouraging evidence in humans, it is possible that further studies will find some forms of prolotherapy helpful in veterinary patients.

Bottom Line
There are a variety of theories behind prolotherapy, some more plausible than others, but there is not yet a clearly established general mechanism. The clinical trial research in humans is mixed and not robust, but there is moderate evidence supporting the effectiveness of prolotherapy for arthritis. There has only been one small animal study, a clinical trial in dogs for elbow and knee arthritis, and it found no benefit.

References

1. Krsti?evi? M, Jeri? M, Došenovi? S, Jeli?i? Kadi? A, Puljak L. Proliferative injection therapy for osteoarthritis: a systematic review. Int Orthop. 2017;41(4):671-679. doi:10.1007/s00264-017-3422-5
2. Rabago D, Slattengren A, Zgierska A. Prolotherapy in primary care practice. Prim Care. 2010;37(1):65-80. doi:10.1016/j.pop.2009.09.013
3. Morath O, Kubosch EJ, Taeymans J, et al. The effect of sclerotherapy and prolotherapy on chronic painful Achilles tendinopathy-a systematic review including meta-analysis. Scand J Med Sci Sports. 2018;28(1):4-15. doi:10.1111/sms.12898
4. Nagori SA, Jose A, Gopalakrishnan V, Roy ID, Chattopadhyay PK, Roychoudhury A. The efficacy of dextrose prolotherapy over placebo for temporomandibular joint hypermobility: A systematic review and meta-analysis. J Oral Rehabil. 2018;45(12):998-1006. doi:10.1111/joor.12698
5. Hung C-Y, Hsiao M-Y, Chang K-V, Han D-S, Wang T-G. Comparative effectiveness of dextrose prolotherapy versus control injections and exercise in the management of osteoarthritis pain: a systematic review and meta-analysis. J Pain Res. 2016;Volume 9:847-857. doi:10.2147/JPR.S118669
6. Hauser RA, Lackner JB, Steilen-Matias D, Harris DK. A Systematic Review of Dextrose Prolotherapy for Chronic Musculoskeletal Pain. Clin Med Insights Arthritis Musculoskelet Disord. 2016;9:CMAMD.S39160. doi:10.4137/CMAMD.S39160
7. Hassan F, Trebinjac S, Murrell WD, Maffulli N. The effectiveness of prolotherapy in treating knee osteoarthritis in adults: a systematic review. Br Med Bull. 2017;122(1):91-108. doi:10.1093/bmb/ldx006
8. Sit RW, Chung VC, Reeves KD, et al. Hypertonic dextrose injections (prolotherapy) in the treatment of symptomatic knee osteoarthritis: A systematic review and meta-analysis. Sci Rep. 2016;6(1):25247. doi:10.1038/srep25247
9. Rabago D, Nourani B. Prolotherapy for Osteoarthritis and Tendinopathy: a Descriptive Review. Curr Rheumatol Rep. 2017;19(6):34. doi:10.1007/s11926-017-0659-3
10. Sherwood JM, Roush JK, Armbrust LJ, Renberg WC. Prospective Evaluation of Intra-Articular Dextrose Prolotherapy for Treatment of Osteoarthritis in Dogs. J Am Anim Hosp Assoc. 2017;53(3):135-142. doi:10.5326/JAAHA-MS-6508

One of the great mysteries of veterinary medicine if hyperthyroidism in cats. Benign tumors of the thyroid glad in older cats can produce excessive amount of thyroid hormone, and this can lead to a host of clinical symptoms. Fortunately, the disease is relatively easily treated by various methods. However, the condition seems to be more common than it used to be a few decades ago (though there are no reliable statistics, and it could just as easily be that vets were less likely to diagnose this problem in the past), so this begs the question of what might be the cause of the apparent increase in cases.

There are many theories, and environmental toxins of one kind of another are a popular focus of blame for this disease. In 2015 I wrote about the claim that certain flame retardant chemicals, known as PBDEs, might be associated with thyroid disease in cats, and I provided an update on the literature about this in 2017. At this point, the best we can say is that there has been some association between PBDE levels and thyroid disease in cats, but it is based on very weak data involving few animals, and no strong evidence yet exists to label this as a causal factor.

I recently ran across a new article by the same research group who looked at PBDEs and thyroid disease in 2016, this time suggesting there might be a connection with a different class of environmental chemicals, known as per- and polyfluoroalkyl substances (PFASs for short).

Miaomiao Wang, Weihong Guo, Steve Gardner, Myrto Petreas, June-Soo Park. Per- and polyfluoroalkyl substances in Northern California cats: Temporal comparison and a possible link to cat hyperthyroidism. Environmental Toxicology and Chemistry, 2018; DOI:

This paper appears to be using blood samples from the same groups of cats discussed in the previous paper, 26 sampled between 2008 and 2010, and 22 sampled between 2012 and 2013. The conclusions are similar but even more tentative than those regarding PBDEs. Levels of the chemicals declined between the earlier sampling period and the later (in humans as well as cats), likely due to the phasing out of these chemicals in industrial use.

There was a statistical associated between PFAS levels and thyroid disease in the latter period, but not in the earlier period. However, there was tremendous individual variation and very few cats in the two groups (those with thyroid disease and those without), so it is impossible to identify a clearly meaningful difference. Whether these chemicals even could be a potential cause for hyperthyroidism is unclear. While some lab animal studies have shown that PFASs can affect thyroid hormone levels, the direction of this effect (towards higher or lower levels) and the real-world significance are not at all clear in ab animals or humans.

Interestingly, there was no apparent association between levels of PFASs and PBDEs in these cats. That means that while PBDEs may have been associated with hyperthyroidism, and PFASs may have been associated with hyperthyroidism, there was no association between PBDEs and PFASs. That doesn’t make a lot of statistical sense, and it is likely an example of the limitations of such a small sample of cats.

While papers like these are interesting, they don’t yet add up to any clear or compelling evidence for a causal role of either of these classes of chemicals in feline hyperthyroidism. If anything, they may suggest such a role is unlikely since the levels of both PFASs and PBDEs seem to be going down over the last 10 years, yet there is no sign that thyroid disease is becoming any less common.

It’s been a few years since I covered the subject of hyperbaric oxygen therapy (HBOT), a treatment that involves placing patients in a sealed chamber and raising the air pressure and oxygen levels above those in the normal atmosphere at sea level. Back in 2013, I summarized the available evidence and reached this conclusion:

HBOT is a biologically plausible therapy with substantial in vitro and animal model research to support possible benefits in a variety of conditions. There is, however, almost no clinical trial evidence to support its use in companion animal species. Justification of veterinary use of HBOT comes only from extrapolation from basic principles, pre-clinical research, anecdote, and extrapolation from research in humans, so this should be viewed as an unproven, experimental veterinary therapy.

There are a few indications for which the human clinical trial research provides at least a moderate degree of confidence that HBOT is effective. There are many others for which there is only limited and low-quality evidence and no clear conclusion can be drawn. Not all uses validated in humans are relevant to veterinary use, and most veterinary applications have not been directly studied in people. Overall, the evidence is strongest for adjunctive use of HBOT to facilitate healing of chronic wounds not resolving with standard therapies.

HBOT is generally quite safe, but there are both minor and serious potential adverse effects, and there is some risk associated with the use of the equipment.

I followed this article with a brief report of warnings from the FDA about unsupported and exaggerated claims for HBOT in humans and a report on a human study showing no benefits for treatment of concussion. Given that I last looked at the literature 5 years ago, I thought it worthwhile to check for any new evidence on this treatment in veterinary patients. Unfortunately, there hasn’t been very much research published since 2013.

A 2017 review by two authors supportive of HBOT concluded:

There is a paucity of data about use of HBOT in veterinary medicine, and no randomized, controlled clinical trials for any condition have been published… HBOT holds therapeutic promise in animals and deserves clinical and research attention. However, the therapy is not benign, and understanding the basics of HBOT and possible complications is critical. Because the clinical information, apart from expert opinion and research experiments with small numbers, remains minimal, research is essential to expand information about the physiology behind the modality, condition-specific treatment parameters, and appropriate and efficacious indications for use in veterinary patients.

Since then, there have been two published veterinary reports. One study evaluated the safety of HBOT by recording any adverse effects noticed during 230 treatments in 12 cats and 78 dogs. Though this was only an observational study of short-term treatment, and there were a few other limitations, no serious adverse effects were seen. Minor effects, suggesting some discomfort and possible inner ear problems, were seen in some patients at a modest rate. This certainly doesn’t rule out the possibility of any more serious harm, and cases of significant injury have been reported in humans. However, this study supports the general findings in the limited veterinary literature that adverse effects of HBOT seem uncommon and typically minor. The only known fatality reported in veterinary HBOT involved an explosion which killed both the patient and the operator at an equine therapy facility in 2012.

There has been one study of HBOT in dogs published since my last review:

Latimer CR, Lux CN, Roberts S. Effects of hyperbaric oxygen therapy on uncomplicated incisional and open wound healing in dogs. Vet Surg. 2018 Aug;47(6):827-836.

This was an experimental study, not a clinical study. Ten lab beagles were given surgical wounds, and then given the same wound care (suturing, bandaging, pain control, etc.) except that 5 were given a series of HBOT treatments as well. Blinded observers evaluated wound healing scores, and biopsies of the wounds were examined. No effect of HBOT was seen, and the wounds healed the same regardless of whether the dogs got HBOT or not.

There are a number of limitations to this study, including the small number of dogs and the use of lab dogs with artificial wounds rather than a real-world population of dogs with the kinds of wounds that would typically be treated with HBOT. Nevertheless, the study certainly suggests there is no dramatic benefit to HBOT in the healing of routine, uncomplicated wounds.

Bottom Line
The literature since 2013 has not provided any reason to alter my original conclusions. While HBOT appears to have promise based on theoretical reasoning, lab animal studies, and some validated uses in humans, there is still no convincing evidence to support any claims of benefits to veterinary patients. While the risks appear to be minimal, there is only weak and unreliable evidence of any benefits. The use of a complex, expensive, and potentially harmful treatment in the absence of any strong evidence for benefits is not the best way to use limited resources in veterinary medicine or to provide the best care to patients. Advocates for HBOT, especially those selling it as part of their practice, ought to focus on supporting rigorous and objective clinical studies to identify what real benefits, if any, there are from this therapy.

I’ve written about placebo effects in animals several times. These appear in both clinical research studies and in real-world medical practice in many different ways. However, one of the most significant phenomena that fools us into thinking useless therapies are working in our pets is the caregiver placebo effect. This is when people, including owners, vets, and researchers, see what they hope and expect to see rather than what is really happening to the animals in their care. Since our pets can’t speak for themselves, we interpret their actions in deciding whether they feel better or worse, and we fool ourselves easily and often.

The classic illustration of the caregiver placebo effect in dogs comes for a study of arthritis medication. When given a placebo, a fake treatment that does nothing at all, about half of owners, and nearly as many vets, saw significant improvement in subjective measures of pain and function. Objective measures, such as the amount of weight a dog puts on an arthritic leg, did not show improvement with placebo because such measures are harder to fool than our unaided observations.

This phenomenon is known from studies of caregivers for human patients as well as for dogs, and last year another paper appeared showing us that the exact same phenomenon affects owners and vets when evaluating pain in cats.

Gruen, M. E., Dorman, D. C., & Lascelles, B. D. X. (2017). Caregiver Placebo Effect in Analgesic Clinical Trials for Painful Cats with Naturally-Occurring Degenerative Joint Disease. The Veterinary Record, 180(19), 473. http://doi.org/10.1136/vr.104168

This review looked at six published clinical trials of treatments for arthritis in cats. They assessed the apparent improvement reported in cats getting a placebo on both subjective and objective measures. What they found was that 50-70% of cats getting placebo (meaning fake, useless treatment) were classified as treatment successes on subjective client measures. This means that a majority of clients truly felt their cats were better just because they mistakenly believed they were given an effective treatment. However, only 10-50% of objective measures showed an improvement with placebo. (the reasons cats may have improved even while getting no treatment at all are other aspects of placebo effects, which I have discussed elsewhere.)

This finding reinforces, yet again, that we cannot trust anecdotes or our own observations to determine if treatments work or not. We need placebo controlled, blinded studies with real, objective measures of effect or we risk making ourselves feel better without actually helping our patients and pets.

The Truth About Pet Cancer (TAPC) is a slick bit of propaganda. Although it contains some interesting, even promising ideas, these are unfortunately served with a heavy seasoning of misinformation and fear-mongering. Hypotheses and opinions are presented as established facts, and anyone who disagrees is suggested to be ignorant at best, venal and corrupt at worst.

You can read my full article on the Science-based Medicine Blog-

What’s the Truth behind The Truth About Pet Cancer?