Platelet Rich Plasma (PRP) for Pets- Does It Work?

A reader recently asked me to take another look at a product for producing and administering platelet rich plasma (PRP). This is a subject I haven’t covered since 2013, when I wrote about a small study looking at the use of PRP for arthritis in dogs. Since that time, there has been a huge increase in the amount of laboratory and human-focused research into the use of platelets as a form of “regenerative medicine.” Much like stem cells, which I have written about more often, PRP is used to treat a wide range of conditions, such as arthritis, connective tissue injuries, wounds, and many others. Like stem cell therapies, there is a plausible rationale for PRP and some encouraging pre-clinical research, but the marketing and use of both approaches have outpaced the clinical research by quite a bit.

The basic principle is that platelets, and other components of blood, contain growth factors, compounds that reduce inflammation, and a host of other agents that could be useful in managing pain and in promoting healing. Studies looking at PRP and some of these components certainly find evidence of physiologic activity that might, in principle, be beneficial to patients. Anyone who has followed this blog or read my book, however, will know that such laboratory studies frequently fail to accurately predict what will happen in the real world of the clinic. Living patients are much more complex and varied than tissue in a test tube, and studies in rats or human cell culture don’t always reflect what happens in living dogs and cats.

The actual clinical research on PRP in veterinary species is sparse and not robust. The best evidence is in horses, and here is the conclusion of a systematic review of some of this research (for treatment of musculoskeletal lesions):

Most experimental studies revealed positive effects of PRP. Although the majority of equine clinical studies yielded positive results, the human clinical trials’ results failed to corroborate these findings. In both species, beneficial results were more frequently observed in studies with a high risk of bias. The use of PRP in musculoskeletal lesions, although safe and promising, has still not shown strong evidence in clinical scenarios.

There are a handful of clinical studies in dogs:

  • Prostatic cysts– This was an uncontrolled study. Ten dogs had their cysts injected with PRP, and eventually they all resolved, but there was no comparison with other treatment or no treatment, so the significance of this in uncertain.
  • Corneal ulcers– This was a randomized, controlled trial adding PRP to conventional therapy for uncomplicated corneal ulcers. No difference was seen in healing between the groups.
  • Supraspinatus tendinopathy-Another uncontrolled study in which ten dogs were treated and some got better while others didn’t. No real conclusion can be drawn from this.
  • Wound healing– This was a small study using three dogs. Eight small (6mm) wounds were created on each dog, and some were treated with PRP while others were not. The authors reported faster healing in the PRP-treated wounds, but there was no blinding, and the assessment of the wounds was subjective, so risk of bias is high.
  • Skin flaps-Another lab study in beagles. Here skin flaps were created on both sides of several dogs, one treated with PRPR and the other not. Some measures of wound healing differed between the treatments and others did not, though the difference in survival of the flaps was pretty large. Again, no blinding was involved, so the risk of bias is high.
  • Bone healing-Some more poor beagles had bone screws placed and some were treated with PRP while others were not. No difference in bone healing was seen.
  • Bone Healing-This time, dogs had a defect surgically created in their radius and then fixed in place, and healing was compared between dogs treated with PRP or untreated. There was a difference in bone healing between the groups, and again some controls for bias were missing. Other lab studies in animals looking at bone healing have found some evidence of benefits, but the conclusions are tentative due to the paucity of studies.

 Overall, the research in dogs is promising but limited, and the most recent review concludes:

The growing development and use of PRP preparations in wound healing and tissue repair in people will require the development of new randomized controlled studies with large sample sizes to establish therapeutic efficacy.

Unsurprisingly, there is even less research on PRP in cats, and no conclusions at all can be drawn about the effectiveness of PRP in this species.

As usual, when the veterinary research is limited, we turn to studies in humans to see whether a therapy is likely to be helpful. While the quantity and quality of human research is inevitably higher than that in dogs and cats, the results cannot reliably be assumed to apply to other species, so such studies can only suggest, not prove the potential benefits of PRP in veterinary patients.

The human clinical trial research is vast, with almost 300 systematic reviews currently listed on Pubmed. The conclusions of these reviews are varied, with some claiming proven benefits while others suggest more research is needed for reliable conclusions or that PRP is not helpful for the condition being evaluated. And many of these reviews apply to conditions that are not relevant to veterinary species. 

I have collected below a sample of the more recent systematic reviews in conditions that might be a target for PRP therapy in veterinary species. This is not an exhaustive list, merely a sample illustrating the variety of conclusions reached about the meaning of the human clinical trial literature. 

Bottom Line

PRP is a plausible therapy, and there is reason to believe it could be helpful for veterinary patients with arthritis, connective tissue and muscle injuries, wounds, and other conditions. However, the clinical trial in humans is encouraging but not consistently positive, and there is very little clinical research in veterinary species. Much of the veterinary research consists of small studies with significant methodological limitations, which means we cannot confidently conclude what conditions, if any, might benefit from treatment with PRP.

As with many veterinary therapies that are insufficiently tested, PRP involves a variety of commercial products which vary in ways which might be significant for their effectiveness but which haven’t been specifically tested in most, if any, of the conditions for which they are marketed.

Few significant signs of harm have been seen in the preliminary PRP research, so risks are likely small, though our confidence in this conclusion must also be limited by the absence of strong research evidence.

Systematic Reviews of Clinical Trials in Humans

Osteoarthritis
Regardless of the positive results obtained in several studies, it is important to take into consideration that many of the referred studies were not randomized and/or blinded controlled trials[11,88,114] and therefore should be regarded with caution. In fact, in a recent meta-analysis, from 10 manuscripts selected for the study, presented high risk of bias [117]. The high heterogeneity among studies is another critical limitation of PRP [118]. In addition, many of these studies suggest that autologous PRP is a safe treatment; however, the potentially negative effects of PRP were not fully investigated at this point.

Acute Muscle Injury
The promising biological rationale, the positive preclinical findings, and the successful early clinical experience of PRP injections are not confirmed by the recent high-level RCTs. Therefore any benefit in terms of pain, function, return to sport, and recurrence using PRP injections for the treatment of acute muscle injuries is not supported. Due to the bias in the studies, the heterogeneity of the findings, and the limited sample size, the evidence should be considered to be of low or very low quality.

TMJ Osteoarthritis-
There is slight evidence for the potential benefits of intra-articular injections of PRP in patients with TMJ-OA. However, a standardized protocol for PRP preparation and application needs to be established.

Orthopedics-
The results of this meta-analysis, which documents the very marginal effectiveness of PRP compared to controls, does not support the use of PRP as conservative treatment in orthopaedics.

Knee osteoarthritis-
Intra-articular PRP injections probably are more efficacious in the treatment of knee OA in terms of pain relief and self-reported function improvement at 3, 6 and 12 months follow-up, compared with other injections, including saline placebo, HA, ozone, and corticosteroids.

Knee osteoarthritis-
In patients with symptomatic knee OA, PRP injection results in significant clinical improvements up to 12 months post injection. Clinical outcomes and WOMAC scores are significantly better after PRP versus HA at 3 to 12 months post injection. There is limited evidence for comparing leukocyte-rich versus leukocyte-poor PRP or PRP versus steroids in this study.

Rotator Cuff Injury-
The results of this meta-analysis do not support the use of platelet-rich plasma/platelet-rich fibrin matrix in patients with rotator cuff injuries.

Knee osteoarthritis-
On the basis of the current evidence, PRP injections reduced pain more effectively than did placebo injections in OA of the knee (level of evidence: limited due to a high risk of bias). This significant effect on pain was also seen when PRP injections were compared with hyaluronic acid injections (level of evidence: moderate due to a generally high risk of bias). Additionally, function improved significantly more when PRP injections were compared with controls (limited to moderate evidence). More large randomised studies of good quality and low risk of bias are needed to test whether PRP injections should be a routine part of management of patients with OA of the knee.

Lateral epicondylitis and rotator cuff injuries-
This review shows that PRP may reduce pain associated with lateral epicondylitis and rotator cuff injuries.

Knee OA-
PRP intra-articular injection of the knee may be an effective alternative treatment for knee OA, especially in patients with mild knee OA. Although some studies suggested that the effect of PRP was no better than HA, we found that it was no worse. A large, multicenter, randomized trial is needed to further assess the efficacy of PRP treatment for patients with knee OA.

Hip OA-
Literature to date concludes that intra-articular platelet-rich plasma injections of the hip, performed under ultrasound guidance to treat hip osteoarthritis, are well tolerated and potentially efficacious in delivering long-term and clinically significant pain reduction and functional improvement in patients with hip osteoarthritis. Larger future trials including a placebo group are required to further evaluate these promising results. Level of evidence: Level I, a systematic review of level I studies.

Knee OA-
This systematic review demonstrated no long-term statistically significant improvement in patient validated outcomes and secondary outcomes both in patients with knee OA or following TKA for OA. However PRP has been shown to have short to medium-term benefits in pain control after TKA and activities of daily living in patients with OA.

Tendinopathy
There is good evidence to support the use of a single injection of LR-PRP under ultrasound guidance in tendinopathy. Both the preparation and intratendinous injection technique of PRP appear to be of great clinical significance.

OA Pain-
Although the results of the included studies showed that arthrocentesis or arthroscopy with PRP or PRGF, saline, or HA injections all reduced pain and increased mouth opening, the evidence was of very low quality. Further studies are needed to confirm these preliminary results showing that PRP or PRGF with arthrocentesis or arthroscopy significantly improved pain but did not increase MMO compared with findings in the control or HA groups.

Knee OA-
IA-PRP is a viable treatment for knee OA and has the potential to lead to symptomatic relief for up to 12 months. There appears to be an increased risk of local adverse reactions after multiple PRP injections. IA-PRP offers better symptomatic relief to patients with early knee degenerative changes, and its use should be considered in patients with knee OA.

Lateral Epicondylitis-
The current best available evidence suggests that CSI improves functional outcomes and pain relief in the short term, while AB and PRP are the most effective treatments in the intermediate term.

Degenerative joint disease-
The analysis showed an increasing number of published studies over time. Preclinical evidence supports the use of PRP injections that might promote a favourable environment for joint tissues healing. Only a few high-quality clinical trials have been published, which showed a clinical improvement limited over time and mainly documented in younger patients not affected by advanced knee degeneration.

Achilles tendinopathy-
The main finding of this study was the paucity of high-level literature regarding the application of PRP in the management of patellar and Achilles tendinopathy. However, the clinical data currently available, although not univocal, suggest considering PRP as a therapeutic option for recalcitrant patellar and Achilles tendinopathies.

Muscle Strain-
Evidence from the current literature, although limited, suggests that the use of PRP may result in an earlier return to sport among patients with acute grade I or II muscle strains without significantly increasing the risk of reinjury at 6 months of follow-up. However, no difference in time to return to sport was revealed when specifically evaluating those with a grade I or II hamstring muscle strain.

Rotator Cuff-
The currently limited available evidence on PRP for nonoperative treatment of chronic rotator cuff disease suggests that in the short term, PRP injections may not be beneficial. When directly compared with exercise therapy, PRP does not result in superior functional outcomes, pain scores, or range of motion. However, interpretation of this literature is confounded by the lack of reporting of the cytology and characteristics of PRP.

After knee replacement-
Current meta-analysis indicates that PRP is associated with increasing the ROM after TKA in short term and long term. What’s more, PRP can also decrease the WOMAC score and pain intensity without increasing the occurrence of infection.

Patellar tendinopathy-
Platelet-rich plasma is a safe and promising therapy in the treatment of recalcitrant PT. However, its superiority over other treatments such as physical therapy remains unproven. Further RCTs are required to determine the relative effectiveness of the many available treatments for PT and to determine the subgroups of patients who stand to gain the most from the use of these therapies.

Lateral epicondylitis-
Corticosteroid injections provide rapid therapeutic effect in the short-term with recurrence of symptoms afterwards, compared to the relatively slower but longer-term effect of platelet-rich plasma.

Lateral epicondylitis-
Local corticosteroid injections demonstrated favorable outcomes compared with those of local PRP treatments for lateral elbow epicondylitis during the short-term follow-up period (4 weeks and 8 weeks post-treatment). Otherwise, at the long-term follow-up (24 weeks post-treatment), PRP injections had improved pain and function more effectively than corticosteroid injections.

Knee OA-
PRP intra-articular injections of the knee may be an effective alternative treatment for knee OA. However, current studies are at best inconclusive regarding the efficacy of the PRP treatment. A large, multicenter randomized trial study is needed to further assess the efficacy of PRP treatment for patients with knee OA.

Knee OA-
In short-term outcomes (?1 year), PRP injection has improved functional outcomes (WOMAC total scores, IKDC score and EQ-VAS) when compared to HA and placebo, but has no statistically significant difference in adverse events when compared to HA and placebo. This study suggests that PRP injection is more efficacious than HA injection and placebo in reducing symptoms and improving function and quality of life. It has the potential to be the treatment of choice in patients with mild-to-moderate OA of the knee who have not responded to conventional treatment.

Epicondylitis, Plantar fasciitis-
The use of PRP yields statistically and clinically better improvement in long-term pain than does CS in the treatment of EE. The use of PRP yields statistically and clinically better long-term functional improvement than that of CS in the treatment of PF.

Tendinopathy-
Although the results of this review show promise for the use of PRP in chronic tendinopathy, the analysis highlighted the need for more controlled clinical trials comparing PRP with placebo.

Hamstring injury-
Meta-analysis showed superior efficacy for rehabilitation exercises. PRP injection had no effect on acute hamstring injury. Limited evidence was found that agility and trunk stabilisation may reduce re-injury rates. The limitations identified in the majority of RCTs should improve the design of new hamstring RCTs.

TMJ OA-
This meta-analysis demonstrated that PRP injection provided adjuvant efficacy to arthrocentesis or arthroscopy in pain reduction for temporomandibular joint osteoarthritis in the long term. Furthermore, PRP injection significantly reduced pain better compared with HA injection, saline injection, or no injection.

Knee OA-
The results of this systematic review and meta-analysis suggest that PRP is superior to HA for symptomatic knee pain at 6 and 12 months. ACP appears to be clearly superior over HA for pain at both 6 and 12 months. There were no advantages of PRP over HA for clinical outcomes at both 6 and 12 months.

Posted in Science-Based Veterinary Medicine | 1 Comment

Assisi Calmer Canine-What’s the Evidence for PEMF Treatment of Separation Anxiety?

I haver written about pulsed-electromagnetic field devices (PEMF) a couple of times before (12). In my most recent review, I concluded:

Despite the fact that there has been interest in the potential medical applications of electricity for over 150 years, and serious scientific research investigating PEMF has been going on for over 50 years, there is surprisingly little robust evidence showing meaningful clinical benefits…PEMF devices are widely used, and this creates the impression that they have been solidly validated, but the reality is more ambiguous…There are very few clinical trials of PEMF in [veterinary] patients. The studies that have been published have not found consistent and convincing evidence of clinically meaningful benefits…The marketing claims of PEMF manufacturers and the excitement of proponents far exceed the strength of the available scientific evidence.

Unfortunately, the lack of evidence is seldom a barrier to aggressive marketing of therapies in veterinary medicine, and this is certainly true for PEMF. What is perhaps more frustrating, is that companies often support or produce small studies with significant limitations as evidence to promote particular uses. These studies are rarely followed, as they should be, by larger, better trials that could be used to justify actual clinical use. 

This certainly appears to be the case for the most well-known veterinary PEMF device, the Assissi Loop. Rather than following up the tentative studies I reviewed for pain, the company has decided to generate yet more weak evidence to justify marketing their device for yet another indication, this time separation anxiety. Their marketing materials are a classic example of claims that go far beyond anything justified by the actual scientific evidence:

The solution” is bad enough, but there had better be some pretty solid clinical research to justify “returns the anxious brain to a more balanced emotional state with long-lasting effects” and “proven to work alone without other treatments or training!” I can’t wait to see the large, robust, long-term clinical trial that shows the Assissi Loop is ready to replace all other separation anxiety therapies and vanquish the disease for ever! So where is it? What? There is no such study?

To call what the company offers as evidence for these dramatic claims underwhelming would be a dramatic understatement. An open-label study lasting six weeks in nine dogs. That’s it! No placebo control, no blinding, no peer-reviewed publication (only a conference report), and a lead investigator who also happens to be the Chief Business Officer of the company selling the product. A pilot trial like this is laden with uncontrolled bias and error, and while it might be enough to justify a real controlled study, it is not even close to sufficient evidence to support the wild marketing claims made for the product. 

I would be thrilled to see a treatment with no detectable adverse effects that could improve or even cure separation anxiety in the vast majority of dogs with 15 minutes of treatment twice a day for six weeks. That would be a miracle, and I would be glad to see it. However, the evidence threshold for miracles in medicine is pretty high, and this study isn’t even close to that threshold. It seems to me inappropriate to make such dramatic promises based on such thin evidence, and it would be more useful for companies such as this to put their resources into supporting rigorous, independent testing of existing claims rather than looking for new markets to create with still more small, limited “pilot” trials.

Posted in General | 2 Comments

New Delaware Rabies Law Undermines the Safety of Pets and the Public

Over the years, one of the most common subjects I have discussed on this blog is vaccination, including their risks and benefits and how pet owners can evaluate them to decide which vaccines are appropriate to give their pets. This is a far more complicated subject than many opponents of vaccination claim. 

It is clear that vaccines, like any medical therapy, can cause harm. However, the evidence for specific types of harm is often poor, and the anxiety about vaccination is often based on fear, not real scientific evidence of real risks. Claims that vaccines cause autoimmune disease (12 or behavioral problems, anxieties about “toxins” such as mercury in vaccines, claims that lower “doses” of vaccines are safer than standard volumes (12), and the value of antibody titers as substitutes for vaccination are all subjects I’ve addressed here. There are few simple, absolute answers, but it is clear that the benefits of vaccination almost always outweigh the risks. However, the anti-vaccine movement is alive and well in veterinary medicine, and vaccine opponents have been all too effective at taking the reasonable concerns pet owners may have about vaccine safety and turning them into unreasonable fear.

In human medicine, we have seen the serious consequences of this fear. Vaccine-preventable diseases are making a comeback, and children are being harmed and killed by illnesses they should never have been allowed to contract. The World Health Organization has listed vaccine hesitancy as one of the top ten public health threats we face. One major element to the growing public health threat of vaccine refusal has been the use of exemptions from vaccine requirements for children attending public schools. While there are uncommon medical reasons to avoid vaccinating some children, exemptions based on the religious or personal belief of parents have reduced vaccine coverage and placed all children at greater risk, those who cannot or will not be vaccinated and even those who are, since vaccine protection is excellent but never perfect. 

In California, non-medical exemptions were prohibited by law in an effort to better protect public health. Unfortunately, anti-vaccine activists were able to undermine the law by seeking exemptions from deluded or unscrupulous physicianswilling to grant exemptions without legitimate medical and scientific foundations. This loophole had to be addressed in additional legislation giving the state health department authority to review medical exemptions when an excessive number of them are issued by an individual doctor or if a specific school has an excessively low vaccine compliance rate. This is an imperfect solution, but the original law has improved vaccination rates in the state, and it is likely the new measures will be somewhat helpful in reducing the risk posed by individual anti-vaccine activists.

In veterinary medicine, most vaccinations are not legally required for most pets. Vaccination rates are lower, and the occurrence of vaccine-preventable disease are consequently higher, than they should be, but the law considers pets to be property, so there is no real movement to require vaccination even if it is clearly in the best interests of the animals. The exception to this is immunization against rabies, which is often required at the state or local level in pets (almost always in dogs, and sometimes in cats and ferrets) because of the risk infected animals present to humans. 

Rabies is almost always fatal, and tens of thousands of people worldwide are killed by it every year. Most of these are exposed by domestic dogs. This is rare in the developed world because of long-standing and successful vaccination campaigns, so many people do not adequately appreciate the danger of reduced vaccine coverage. 

Medical exemptions to rabies vaccination are sometimes sought for pets with a history of adverse reactions to rabies vaccine, with conditions that might be exacerbated by vaccination such as autoimmune disease, and of course for many illegitimate reasons such as age or simply the owner’s perception that the vaccine is unsafe or not necessary. Local government often has discretion as to whether to grant such exemptions, and the process and criteria are variable and inconsistent. Anti-vaccine advocates have long wanted to reduce vaccination against rabies (and other diseases), and for the first time a state-level law has been passed which would facilitate this.

The state legislature in Delaware has passed a law allowing veterinarians to exempt individual dogs, cats, and ferrets from rabies vaccine requirements. This law is, unfortunately, a blank check to anti-vaccine vets that contains no protections against the kind of abuse and deception that has plagued efforts to improve compliance with vaccine mandates in humans. The law states:

Exemption from vaccination against rabies may be permitted if a licensed veterinarian has examined the animal and based on the veterinarian’s professional judgment, has certified in writing that at the time, vaccination would endanger the animal’s health because of its infirmity, disability, illness, or other medical considerations.

This allows complete personal discretion on the part of the veterinarian to determine whether or not a pet should be vaccinated without regard to any legitimate scientific standards. Plenty of alternative medicine vets have completely unscientific beliefs about the risks of vaccines, and these doctors will be able to exempt any pet from vaccination based solely on these beliefs. And if clients demand exemptions for reasons that are not scientifically valid, vets will undoubtedly feel pressured to grant them. There are no rules or constraints they can use as justification for denying illegitimate requests.

The law also makes reference to rabies titer testing. It has been argued that since a high rabies titer likely indicates protective immunity in most pets (some challenge testing has been done for this disease), titers could be used in lieu of vaccination in some cases. This is a reasonable argument, and if clear requirements for running and interpreting antibody titers were made, they might be an appropriate alternative to vaccination on a fixed schedule. However, this law does not address any of these issues and merely states that titers can be done, presumably however the individual veterinarian wants.

A titer test, in the case of these medical exemptions, may be administered to assist in determining the need for the vaccination.

This is entirely meaningless since it does not require a titer or define how titers should be measured or used to determine immune status. The complete lack of any input on this law by informed scientific experts in the subject is clear here. 

The law is titled “Maggie’s Pet Vaccine Protection Act.” The name refers to a pet whose owner believes her dog died from adverse effects of vaccination. This anecdote is tragic, but it does not demonstrate the owner’s belief to be true. The medical expertise behind the act comes from Dr. John Robb, an anti-vaccine zealot who has been at war against vaccination and much of the veterinary profession for years. Dr. Robb is an example of the kind of veterinarian who will use this new law to reduce the protection against rabies that vaccination provide both pets and humans based only on his own passionate but completely unscientific beliefs about vaccines. 

Reasonable changes to vaccination laws based on sound science are totally appropriate. It may be that titers are an effective substitute for vaccination in some cases. However, ill-considered and sloppy laws like this driven by passionate misconceptions about vaccines can only endanger pets and humans. This law is not in the best interests of companion animals or public health, and it is sad that the true danger of such antivaccine activism and laws such as this will only be clear once pets and people start dying of rabies in the U.S. as they do in places where vaccination is not available of common.

Posted in Law, Regulation, and Politics, Vaccines | 25 Comments

Snake Oil Tumexal and Purveyor Jonathan Nyce Finally Face the Law

Over the years, I have written about many quack medical products for veterinary patients, and about many veterinarians and others who sell or use these products with impunity despite laws intended to protect pets and pet owners from ineffective or harmful snake oil. Unfortunately, these laws are weak and rarely enforced, and even when regulators take action, it doesn’t seem to deter illegal and fraudulent behavior. 

Dr. Gloria Dodd was sanctioned by the California Veterinary Medical Board and warned by the FDA, yet she continued her practices until the end of her life, and her business is still active. Dr. Andrew Jones was sanctioned by authorities and gave up his medical license, yet he thrives as an internet entrepreneur. Dr. Al Plechner had a long career providing dangerous treatment based on untested and unscientific ideas, and though at the end of his life was he being investigated by the veterinary medical board, others continue to promote his practices. The bogus supplement Renavast was banned by the FDA, yet continues to be made and sold in the U.S. under a new name.

The seemingly endless list of people and products that freely and repeatedly violate not only any reasonable scientific standard for a medical therapy but often specific laws intended to protect consumers from quack medicines, make it is easy to feel that the effort to promote science-based medicine is entirely futile. However, every once in a while, under the rarest and most extreme of circumstances, a little glimmer of hope shines through. Today, that glimmer comes from the U.S. Attorney’s Office for the Eastern District of Pennsylvania.

United States Attorney William M. McSwain announced that Jonathan Nyce, 70, of Collegeville, PA, was charged by Indictment with wire fraud and the interstate shipment of misbranded animal drugs. The charges arise from a years-long scheme to defraud pet owners of money by falsely claiming to sell canine cancer-curing drugs.

“The defendant’s alleged conduct here is shameful,” said U.S. Attorney McSwain. “As any dog owner will tell you – myself included – pets quickly become part of the family. And when they become sick, caring owners look for hope, often doing everything they can to keep their beloved pets alive and well. The defendant is charged with taking advantage of that nurturing instinct in the worst way possible by defrauding pet owners and giving them false hope that they might be able to save their dying pet. That is both cruel and illegal, and now the defendant will face the consequences.”

I wrote about Tumexal, and Mr. Nyce, back in 2014. While I chose to ignore the irrelevant salacious details of Mr. Nyce’s personal life, I pointed out that his claims about Tumexal included many of the classic warning signs of quackery, and that it was highly improbable that his claims were true or that his product was effective. A superficial evaluation of the product web site showed many reasons to reject it as snake oil out of hand, and a further investigation into the claims and Mr. Nyce’s background made it even clearer that the person and the product should not be trusted.

Despite this, the product website was active from 2013 to 2018, and tens of thousands of dollars were made selling this product to vulnerable pet owners. My satisfaction at seeing this fraud brought to an end is diminished somewhat by how long it took to accomplish and by all the similar fraud that seems to continue unimpeded by law enforcement. And I will be honest, I have concerns that ultimately Mr. Nyce will escape conviction or punishment and eventually return to selling snake oil through some exploitable weakness in the legal case against him.

According to the U.S. Attorney’s Office press release, “’American pet owners rely on the FDA to ensure their pets’ drugs are safe and effective,’ said Special Agent in Charge Mark McCormack, FDA Office of Criminal Investigations’ Metro Washington Field Office.  ‘We will continue to investigate and bring to justice those who ignore or attempt to circumvent the law.’”

I appreciate the sentiment, but I have doubts about the effectiveness of its execution.

Posted in Herbs and Supplements, Law, Regulation, and Politics | 1 Comment

Ketogenic Diets for Dogs and Cats

Nutritional therapies and dietary fads for humans often find their way into veterinary medicine. Sometimes, there is a plausible physiologic rationale or encouraging lab animal research to justify testing specific dietary interventions in dogs and cats, and such interventions may eventually demonstrate meaningful clinical benefits. Dietary interventions for renal disease and urolithiasis, for example, are supported by both pre-clinical and clinical trial data.

Unfortunately, it is common for dietary practices in humans to become popular in veterinary patients even when there is little real evidence to support them or when physiologic differences between humans and companion animals make extrapolations from human nutrition science unreliable. The popularity of grain-free dog foods, for example, is likely explained at least in part by a cultural obsession with the supposed dangers of gluten, despite a lack of evidence to support most of these fears. This now appears to have led to real harm for some dogs who have developed diet-associated cardiomyopathy on these foods.1

One of the many extreme diets for humans that is sometimes promoted as having health benefits for veterinary patient as well is the ketogenic diet. There are groups of activists and veterinarians claiming that ketogenic diets have dramatic benefits for dogs with cancer.2 There is also interest in the potential use of ketogenic diets for epileptic veterinary patients.3–5 In this article, I will briefly review the rationale and evidence for therapeutic use of ketogenic diets.

What is a ketogenic diet?

Ketosis is a physiologic state in which metabolism of carbohydrates is reduced and metabolism of fatty acids is increased, producing elevated levels of ketones, such as acetoacetate and ?-hydroxybutyrate (?OHB). Ketogenic diets are diets which induce a state of ketosis, and they are typically high in fat, low in carbohydrates, and calorie restricted. Ketosis is readily induced in humans by high-fat diets and even short periods of calorie restriction. 

Dogs metabolize ketones much more rapidly than humans. It is difficult to induce a state of ketosis with high-fat diets, and much more prolonged periods of caloric restriction are required. However, ketosis can be induced in dogs using dietary fats that are high in certain
medium-chain triglycerides (MCTs).6–8

How does it work?

There are many theories about how ketosis might have beneficial impacts of specific health problems. Ketogenic diets are obviously useful in weight loss because they are calorie restricted, but there is also some evidence that they may suppress appetite more than other kinds of low-calorie diets.9

Ketosis may be neuroprotective due to specific effects of ketones on neurons. There is some evidence that ketone bodies have direct anticonvulsant activity, and the alterations in neuronal metabolism and neurotransmitter function in ketosis may also be beneficial in some conditions. There are even hypotheses that the effect of ketosis on neurons may be mediated by changes in the gut microbiome induced by ketogenic diets. However, there is no clearly proven or widely accepted mechanism for the neuroprotective effects of ketones.10  

It has been known since the 1920s than many cancer cells rely preferentially on glycolysis for energy, which has led to speculation that ketosis may be beneficial in slowing cancer growth or metastasis.11

What is the evidence for benefits?

There have been extensive in vitro and animal model studies of ketogenic diets, predominantly intended to evaluate their utility in treating epilepsy and cancer. Such studies have, not surprisingly, shown variable results for different diets, indications, and specific animal models. Overall, however, there is reasonable evidence of this kind to suggest ketogenic diets could be useful in treatment of epilepsy, neurodegenerative disorders, and some cancers.10–12

The clinical trial literature in humans based on this preclinical work has been encouraging for some conditions, though it is rarely clear and conclusive. Systematic reviews of studies evaluating ketogenic diets as a therapy for refractory epilepsy in children do show evidence of efficacy in some patients.13–15 The most recent Cochrane review reports, “promising results for the use of [ketogenic diets] in epilepsy. However, the limited number of studies, small sample sizes and the limited studies in adults, resulted in a low to very low overall quality of evidence.”13 Unfortunately, despite some evidence of benefits in seizure control, long-term compliance with ketogenic dietary therapy is often very poor, due inconsistent efficacy and significant adverse effects.13,16

There is less evidence to support claims that ketogenic diets have meaningful benefits in human cancer patients. Though there are promising initial results in studies evaluating ketogenic diets for adjunctive treatment of malignant glioma, “because of the paucity of clinical data, the efficacy of [ketogenic diets] for improving survival and quality of life of glioma patients remains to be proven.”17 In terms of other cancers, “evidence supporting the effects of isocaloric ketogenic dietary regimes on tumor development and progression as well as reduction in side effects of cancer therapy is missing…more robust and consistent clinical evidence is necessary before [ketogenic diets] can be recommended for any single cancer diagnosis or as an adjunct therapy.”18

The evidence base is, as always, far more limited in veterinary patients. There are no published clinical studies evaluating therapeutic ketogenic diets in cats. There are a couple of studies evaluating diets high in MCTs in dogs. One study in dogs with epilepsy found that the test diet did induce higher levels of ?OHB than the control diet, however there was no difference in seizure frequency between the groups.4 In both the test and control groups, 30% of the dogs showed a >/= 50% decrease in seizure frequency, which is consistent with the results of other studies for dogs receiving placebo.4,19

In another study, there was a statistically significant difference in the seizure frequency between dogs eating an MCT-rich diet compared with a control diet, though the mean difference was 0.36 seizures per month, which may not be clinically meaningful. Other measures of seizure frequency also differed between the diets, but the effect seemed inconsistent among individuals. While 3 of 21 dogs had complete cessation of seizures and 7 of 21 had a >/= 50% reduction in seizure frequency, 6 of 21 actually had an increase in seizures on the test diet.5

One study has reported improvements in cognitive function testing for aged lab beagles on a ketogenic diet, but there are no studies evaluating impact on function or quality of life in dogs with naturally occurring cognitive dysfunction.20 There are also no published clinical trials evaluating ketogenic diets as treatments for cancer in dogs.

What are the risks?

In humans, long-term compliance with ketogenic diets is often poor due to a combination of lack of efficacy in some individuals, poor palatability, and adverse effects. Gastrointestinal symptoms, pancreatitis, nutritional deficiencies and deficiency diseases, cardiac disease, urolithiasis, and other adverse effects have been reported in humans on therapeutic ketogenic diets.13,16,18,21–24 The safety of these diets in veterinary patients is unclear due to a lack of relevant research evidence.

Bottom Line

Ketogenic diets have been shown to reduce seizures some human patients with epilepsy. There is preliminary evidence such diets may be beneficial in slowing progression of some kinds of cancer, but there are no clear or reliable clinical trial results demonstrating this. There are clear risks to ketogenic diets in humans that limit their use, and long-term compliance is very poor.

There is no compelling research evidence in dogs or cats showing a clinical benefit to ketogenic diets. Despite the dramatic anecdotal claims made by some proponents of these diets, there is currently insufficient evidence to support recommending therapeutic ketogenic diets in companion animals.

References

1.        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

2.        Nosek J. Could a Change in Diet Cure Your Dog’s Cancer? Mod Dog Mag. May 2019.

3.        Larsen JA, Owens TJ, Fascetti AJ. Nutritional management of idiopathic epilepsy in dogs. J Am Vet Med Assoc. 2014;245(5):504-508. doi:10.2460/javma.245.5.504

4.        Patterson E, Munana K, Kirk C, et al. Results of ketogenic food trial for dogs with idiopathic epilepsy. [abstract]. J Vet Intern Med. 2005;19:421.

5.        Law TH, Davies ESS, Pan Y, Zanghi B, Want E, Volk HA. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy. Br J Nutr. 2015;114(9):1438-1447. doi:10.1017/S000711451500313X

6.        Weeth L. Ketogenic diets for dogs: Treend or Truth? In: VMX 2019 Veterinary Meeting and Expo. Orlando, FL; 2019.

7.        Pi-Sunyer FX. Starvation-Induced Ketosis: Reduction in Dogs Enriched with Odd-Carbon Fatty Acids. Exp Biol Med. 1974;145(3):786-789. doi:10.3181/00379727-145-37895

8.        Crandall LA. A comparison of ketosis in man and the dog. J Biol Chem. 1941;138:123-128. http://www.jbc.org/content/138/1/123.citation. Accessed November 15, 2019.

9.        Castellana M, Conte E, Cignarelli A, et al. Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis. Rev Endocr Metab Disord. November 2019. doi:10.1007/s11154-019-09514-y

10.      D’Andrea Meira I, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. Ketogenic Diet and Epilepsy: What We Know So Far. Front Neurosci. 2019;13:5. doi:10.3389/fnins.2019.00005

11.      Weber DD, Aminazdeh-Gohari S, Kofler B. Ketogenic diet in cancer therapy. Aging (Albany NY). 2018;10(2):164-165. doi:10.18632/aging.101382

12.      Khodadadi S, Sobhani N, Mirshekar S, et al. Tumor cells growth and survival time with the ketogenic diet in animal models: A systematic review. Int J Prev Med. 2017;8(1):35. doi:10.4103/2008-7802.207035

13.      Martin-McGill KJ, Jackson CF, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2018;11:CD001903. doi:10.1002/14651858.CD001903.pub4

14.      Martin K, Jackson CF, Levy RG, Cooper PN. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2016;2:CD001903. doi:10.1002/14651858.CD001903.pub3

15.      Araya-Quintanilla F, Celis-Rosati A, Rodriguez-Leiva C, Silva-Navarro C, Silva-Pinto Y, Toro-Jeria B. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review]. Rev Neurol. 2016;62(10):439-448. http://www.ncbi.nlm.nih.gov/pubmed/27149186. Accessed November 15, 2019.

16.      Cai Q-Y, Zhou Z-J, Luo R, et al. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr. 2017;13(6):528-536. doi:10.1007/s12519-017-0053-2

17.      Noorlag L, De Vos FY, Kok A, et al. Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. Clin Nutr. 2019;38(5):1986-1994. doi:10.1016/j.clnu.2018.10.024

18.      Erickson N, Boscheri A, Linke B, Huebner J. Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol. 2017;34(5):72. doi:10.1007/s12032-017-0930-5

19.      Munana KR, Zhang D, Patterson EE. Placebo Effect in Canine Epilepsy Trials. J Vet Intern Med. 2010;24(1):166-170. doi:10.1111/j.1939-1676.2009.0407.x

20.      Pan Y, Larson B, Araujo JA, et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr. 2010;103(12):1746-1754. doi:10.1017/S0007114510000097

21.      Bergqvist AC, Schall JI, Stallings VA, Zemel BS. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr. 2008;88(6):1678-1684. doi:10.3945/ajcn.2008.26099

22.      Choi JN, Song JE, Shin J Il, Kim HD, Kim MJ, Lee JS. Renal stone associated with the ketogenic diet in a 5-year old girl with intractable epilepsy. Yonsei Med J. 2010;51(3):457-459. doi:10.3349/ymj.2010.51.3.457

23.      Willmott NS, Bryan RAE. Case report: scurvy in an epileptic child on a ketogenic diet with oral complications. Eur Arch Paediatr Dent. 2008;9(3):148-152. doi:10.1007/bf03262627

24.      Bank IM, Shemie SD, Rosenblatt B, Bernard C, Mackie AS. Sudden cardiac death in association with the ketogenic diet. Pediatr Neurol. 2008;39(6):429-431. doi:10.1016/j.pediatrneurol.2008.08.013

Posted in Nutrition | 1 Comment

Cone of Shame Podcast Interview- Placebos for Pets? The Truth about Alternative Medicine for Animals

Dr. Andy Roark and I had a great conversation about my book, Placebos for Pets? The Truth about Alternative Medicine for Animals, and all sorts of related subjects, from evidence-based medicine, to caregiver placebo effects, to acupuncture. Check it out!

Posted in Presentations, Lectures, Publications & Interviews | Leave a comment

New Evidence about When to Neuter Your Dog

I have followed the literature on the risks and benefits of neutering for many years, from writing my own literature review in 2010 to critically analyzing individual research studies on the subject here. The evidence is always growing and changing, and the attitudes of pet owners and veterinarians shift over time. When I started working as a veterinarian almost 20 years ago, routine neutering of all dogs and cats at about 6 months of age was still the dominant and recommended practice. There wasn’t much specific scientific evidence for or against this timing, and the focus of most debate about it was whether or not neutering earlier was better or worse (the evidence suggests there isn’t much difference).1–3

More recently, a series of studies have looked at health outcomes in dogs neutered at or before the traditional age and later than the traditional age.4–6 The initial papers focused on only a few breeds (golden retrievers, Labrador retrievers, and German shepherds), and they had a number of other limitations that made generalizing to neutering for all dogs or cats unreliable. I’ve discussed these individual papers in detail previously. 

A reasonable interpretation of these studies would be that there are some risks of neutering in some breeds, particularly in raising the incidence of diseases those breeds are already pre-disposed to. Earlier neutering might be a factor in this, though if you look at the studies in detail, this association doesn’t hold consistently. Some risks are seen, for example, inn golden retrievers but not Labradors, or in female dogs but not males, or in dogs neutered before 6 months or after 12 months of age but not between these ages. 

All-in-all, these studies should be viewed as evidence that the relationship between breed, size, sex, neutering and various health conditions is complex and hard to predict. No simple, one-size-fits all approach is likely to be optimal for everyone, whether it is traditional neutering at 6 months of age or alternative approaches.

Unfortunately, many people have gone well beyond such reasonable interpretations and used these studies to suggest no dogs should be neutered before 1-2 years of age, or that they should not be neutered at all. Some more extreme voices have even claimed these studies show neutering causes cancer or has other dire health effects. Such excessive claims risk causing harm when pet owners avoid the benefits of neutering out of fear of unlikely risks.

The group whose research has been most influential in changing attitudes about neutering has recently published a brief summary of a much more extensive research project that will hopefully be published in full this year. This more detailed study includes an additional 32 breeds, and the findings illustrate how complex and nuanced the issue is and how unreliable broad, rigid approaches are.

According to the authors, “Considering the occurrence of joint disorders…it is evident that vulnerability to early neutering is related to body size,” with both purebred and mixed small-breed dogs not showing the increased risk with early neutering previously reported in larger breeds.7 The issue of cruciate ruptures and hip dysplasia and other orthopedic diseases that may be influenced by neutering appear only to be a significant consideration in larger breeds which are already prone to these diseases.

Similarly, previous studies have suggested neutering, especially at an early age, may be associated with greater risk of some cancers. However, this risk varies dramatically by sex and breed, with differences seen between male and female golden retrievers, between golden retrievers and Labrador retrievers, and so on. The new evidence makes this variability even clearer. The researchers report no association between early neutering and cancer in mixed-breed dogs and, “in small-breed dogs, with the exception of the Shih Tzu, there was no association between cancer incidence and spaying at any age.”7 So much for the “neutering causes cancer” claim.

In making decisions about neutering, as with any other medical intervention, the key is to balance risks and benefits in the context of the best available evidence. As the evidence changes, we have to be willing to change our positions. I once recommended routine neutering at 6 months for all dogs and cats. I now tend to suggest that there are few medical benefits to neutering male dogs who don’t exhibit certain behavior problems, and these benefits may be offset by some risks in some breeds, especially larger breeds. For female dogs, the benefits of preventing mammary cancer and uterine infections still likely outweigh the risks in most dogs, but in breeds like golden retrievers who are at risk for some cancers that seem to be more common in neutered females, neutering later may have advantages. 

None of these are rigid, universal rules, and we must always consider the unique needs and circumstances of each animal. However, broad claims that we should never neuter or should always wait until some specific age are no more reasonable than broad claims that we should always neuter everybody at 6 months old, and our pets and patients will be better off if we move away from such simplistic thinking and consider the scientific evidence in all its complexity.

References

1.        Howe LM. Short-term results and complications of prepubertal gonadectomy in cats and dogs. J Am Vet Med Assoc. 1997;211(1):57-62. http://www.ncbi.nlm.nih.gov/pubmed/9215412. Accessed January 3, 2019.

2.        Olson PN, Kustritz M V, Johnston SD. Early-age neutering of dogs and cats in the United States (a review). J Reprod Fertil Suppl. 2001;57:223-232. http://www.ncbi.nlm.nih.gov/pubmed/11787153. Accessed January 5, 2020.

3.        Stubbs WP, Bloomberg MS, Scruggs SL, Shille VM, Lane TJ. Effects of prepubertal gonadectomy on physical and behavioral development in cats. J Am Vet Med Assoc. 1996;209(11):1864-1871.

4.        Torres de la Riva G, Hart BL, Farver TB, et al. Neutering Dogs: Effects on Joint Disorders and Cancers in Golden Retrievers. Williams BO, ed. PLoS One. 2013;8(2):e55937. doi:10.1371/journal.pone.0055937

5.        Hart BL, Hart LA, Thigpen AP, Willits NH. Long-term health effects of neutering dogs: comparison of Labrador Retrievers with Golden Retrievers. Coulombe RA, ed. PLoS One. 2014;9(7):e102241. doi:10.1371/journal.pone.0102241

6.        Hart BL, Hart LA, Thigpen AP, Willits NH. Neutering of German Shepherd Dogs: associated joint disorders, cancers and urinary incontinence. Vet Med Sci. 2016;2(3):191-199. doi:10.1002/vms3.34

7.        Hart B, Hart L, Thigpen A, Willits N. Best age for spay and neuter: A new paradigm. Clin Theriogenology. 2019;3(11):235-237.

Posted in Science-Based Veterinary Medicine | 13 Comments

Reviews of Placebos for Pets? The Truth about Alternative Medicine for Animals

People have been writing some great reviews of Placebos for Pets, so I thought I’d share a few. If you liked it, please take a minute to add a review on Amazon or Goodreads and help spread the word. Thanks!

“I highly recommend this book. It’s well worth reading even if you don’t have a pet. It is well-written and easy to read… It’s a useful compendium of information on alternative medicine for animals, and it teaches readers how to figure out for themselves whether they can believe a new health claim. Since I know animals can’t read or speak for themselves, I will speak out for them: thank you, Brennen McKenzie, for this book, and for all your hard work and clear thinking!”
Harriet Hall, MD
Science-based Medicine Blog

“This is a great book for all pet owners, pet professionals, and others interested in animals who need help sifting through all the information on alternative veterinary medicine…His writing style is clear and down to earth, and he explains some very difficult concepts with grace… Reading this was a landmark life experience. Not only did I learn about a lot of specific alternative veterinary practices…I certainly added a few critical thinking tools to my toolbox!”
Eileen Anderson
Author, Remember Me?: Loving and Caring for a Dog with Canine Cognitive Dysfunction

“Just finished my copy this morning and couldn’t wait to post a review! This book is simply a must-read for veterinarians, veterinary team members, and pet owners of all shapes and sizes!

Beyond simply dismissing alternative medicine for animals, Dr. McKenzie provides a wealth of details and references in each chapter. From homeopathy to cold lasers to dietary supplements, his approach of “What is It?”, “Does It Work?” and “Is It Safe?” provides the reader with an easy to understand methodology of assessing the wide range of alternative veterinary medicine practices.

As someone who spends a great deal of time helping to educate and develop veterinary staff, this book will be an invaluable resource in helping me teach our teams about scientific method and sound reasoning.”
TFD, reader review

“A clear-eyed look at how science, which underpins veterinary medicine, can either be the logical basis for how it is practiced, or sometimes be the antithesis of certain veterinary practices. There’s irony in the book’s message, not least of which being why some veterinarians may so willingly suspend disbelief in adopting some of these techniques. We ought to inherently grasp that there really is no such thing as alternative medicine, only that medicine which works, and which has a basis in science, and that which some wish would work, but either doesn’t or is as yet unproven. What we offer to the public for compensation ought to be strictly from among the former. Placebos for Pets makes this all clear. Nicely written and referenced.”
Arnold Goldman, DVM, MPH

“This is a fabulous book. The author explains in laymans terms exactly what the issues are and a very easy to understand explanation of the scientific facts surrounding the more ‘popular’ placebos. I think that this book would be just as useful to help you explain to your pseudoscientific friends and relatives exactly what it is that they’re buying.”
Mike Fairburn, reader review

Posted in Presentations, Lectures, Publications & Interviews | 1 Comment

From SkeptVet TV- Pot for Pets?

My latest video from SkeptVet TV briefly reviews the evidence for cannabis-based health products for pets. You can find more detail here:

SkeptVet Blog posts on cannabis

Veterinary Practice News columns on cannabis (1, 2)

Posted in SkeptVet TV | 1 Comment

Evidence Update- Do PEMF Devices like the Assisi Loop Work?

Introduction
Since the discovery of electricity and magnetism, these mysterious forces have been thought to have healing powers. Many fanciful electrical devices were promoted in the nineteenth and early twentieth century as cures for diverse ailments or general health tonics.1 More serious scientific research into the effects of electromagnetic fields on tissues and animals began in the 1930s, and by the 1980s there was sufficient evidence for some kinds of pulsed electromagnetic filed (PEMF) devices to be approved by the FDA for use in human patients.2

Since then, a large number of PEMF devices have been marketed for both human and veterinary medical use. The scientific evidence behind these devices, from in vitro and animal model studies to clinical trials, is complex and inconsistent. Pubmed lists about 50 systematic reviews covering nearly 200 clinical trials, and there well over 1,000 articles if one includes preclinical laboratory studies. PEMF devices use a variety of designs and treatment protocols for a wide range of medical conditions, so any generalizations about the efficacy of these devices are necessarily tenuous. However, because PEMF devices are aggressively marketed to veterinarians and animal owners, some assessment of the evidence behind them is necessary.

It’s been ten years since my first review of this subject, and there was little evidence to support claims for veterinary PEMF devices at the time. Though this is still the case, some new evidence is available.

Pre-clinical Evidence
There is a large scientific literature showing that electromagnetic fields have interesting and potentially significant biological effects on animal cells and tissues. PEMF devices can affect the levels of calcium and nitric oxide in tissues, which can influence extensive and complex pathways involved in metabolism, inflammation, pain transduction, tissue growth and repair, and many other biological activities. PEMF devices have also been shown to affect gene expression, vasomotor tone, and many other physiologic processes.2–5 These studies show the potential for clinically relevant benefits from PEMF treatment. 

Lab animal studies also show effects of PEMF treatment that may be useful to clinical patients, though there is great variation in the treatment used and the results. Some evidence suggests benefits in soft-tissue and bone healing, though not all of the research is positive.2,6–8

However, it is important to understand that such in vitro and animal model findings are not sufficient to justify clinical use. Many therapies, from pharmaceuticals to manual therapies to other high-tech treatments such as low-level laser, have demonstrable effects on tissues that often do not translate into meaningful clinical benefits for patients. Clinical trials are always necessary before making confident claims for any medical therapy.

Human Clinical Trial Evidence
Though there are hundreds of clinical studies in humans for PEMF in various indications, the results are mixed and difficult to interpret. For example, there are some studies showing meaningful improvements in post-operative pain in human patients undergoing breast augmentation surgery.9,10 However, systematic reviews of studies evaluating PEMF for pain associated with osteoarthritis of the knee are mixed, with some showing no effect,11 some inconclusive,12–15 and others suggesting some benefit.16 Strong generalizations about the efficacy of PEMF for pain aren’t justified based on a literature incorporating varied treatment protocols for different indications with mixed results.

The same inconsistency exists in studies of bone healing17–20 and other clinical uses in humans.21–23 There is evidence of benefits, but it is inconsistent, and the strength of this evidence is limited by heterogeneity in treatment protocols and indications as well as by methodological weaknesses in clinical trials. 

As always, clinical trial evidence for specific indications in veterinary patients is the most relevant type of evidence for veterinarians choosing which treatments to adopt. The clinical trial literature for PEMF is currently very sparse, but there are some studies we can evaluate.

Veterinary Clinical Trials
Though some encouraging case studies and uncontrolled studies have been published,24 there have been only a few controlled clinical trials of PEMF treatment in veterinary patients. 

A small pilot study randomly divided 16 dogs undergoing ovariohysterectomy into four groups- IV saline, IV saline and PEMF, IV morphine, and IV morphine and PEMF. For 6 hours after extubation, a variety of physiologic variables were measured, including heart and respiratory rates and blood pressure, and a validated pain scale was employed by a blinded observer. There were a couple of statistical differences in blood pressure at some time points, but no identifiable analgesic effect of PEMF. The small number of animals in each group likely made the study underpowered to detect all but the most dramatic effects.25

A 2018 study evaluated the use of a PEMF device in 16 dogs undergoing hemilaminectomy for naturally-occurring intervertebral disk disease (IVDD).26 Eight dogs were randomized to active or sham PEMF treatment and evaluated in terms of a primary outcome (gait) and numerous secondary outcomes involving neurologic status, function, and pain. There was no benefit detected in the primary outcome or in the majority of secondary outcomes. 

Placing responses and one measure of pain at the surgical site did appear improved in the PEMF group compared to the control. However, when multiple secondary outcomes are evaluated in a clinical study, it is common for some differences to appear by chance despite statistical efforts to control for this,27 and the authors state that these findings “should be interpreted with caution.”26

The most recent veterinary clinical trial also used IVDD patients as subjects.28 Fifty-three patients were randomly assigned to active or sham PEMF treatment and evaluated in the hospital and by owners at home for up to 6 weeks after surgery. There were no apparent benefits in terms of pain or function as assessed by owners or clinicians, though post-hoc power calculations indicated the study was not sufficiently powered to detect some of these differences. There were some small differences in long-term appearance of surgical wounds, though all wounds healed appropriately. Owners also gave slightly more pain medication to dogs in the control group than the PEMF group, though pain was not rated differently between the groups.

Bottom Line
Despite the fact that there has been interest in the potential medical applications of electricity for over 150 years, and serious scientific research investigating PEMF has been going on for over 50 years, there is surprisingly little robust evidence showing meaningful clinical benefits. We know a lot about the physiologic effects of PEMF, and preclinical research suggests a number of clinical applications. There is clinical trial evidence from humans showing potential benefits for bone and soft-tissue healing, pain reduction, and other uses, but this evidence is inconsistent and complicated by the use of many different devices and treatment protocols. PEMF devices are widely used, and this creates the impression that they have been solidly validated, but the reality is more ambiguous. 

There is also preclinical research in veterinary species showing physiological effects from PEMF devices and potential clinical applications. However, there are very few clinical trials of PEMF in actual patients. The studies that have been published have not found consistent and convincing evidence of clinically meaningful benefits. Many outcome measures have shown no effect of PEMF, though a few have shown effects that might be meaningful. If additional independent trials confirm such potential benefits, it may be possible to have confidence in some clinical uses of PEMF. For now, however, the marketing claims of PEMF manufacturers and the excitement of proponents far exceed the strength of the available scientific evidence.

It is also worth noting that most studies of PEMF devices in human and veterinary patients have found few, if any, adverse effects. While this is reassuring, it also calls into question the real potency of these devices. Medical treatments with important and dramatic benefits that have no meaningful side effects and extremely rare, and it is more common to find that the absence of adverse effects indicates the absence of any meaningful clinical effects at all.

References

1.        Kang L, Pedersen N. Quackery: A Brief History of the Worst Ways to Cure Everything. New York, NY: Workman Publishing, Inc.; 2017.

2.        Gaynor JS, Hagberg S, Gurfein BT. Veterinary applications of pulsed electromagnetic field therapy. Res Vet Sci. 2018;119:1-8. doi:10.1016/j.rvsc.2018.05.005

3.        Fini M, Giavaresi G, Carpi A, Nicolini A, Setti S, Giardino R. Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies. Biomed Pharmacother. 2005;59(7):388-394. doi:10.1016/j.biopha.2005.02.002

4.        Yuan J, Xin F, Jiang W. Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair. Cell Physiol Biochem. 2018;46(4):1581-1594. doi:10.1159/000489206

5.        Pilla AA. Nonthermal electromagnetic fields: From first messenger to therapeutic applications. Electromagn Biol Med. 2013;32(2):123-136. doi:10.3109/15368378.2013.776335

6.        Kwan R, Lu S, Choi H, Kloth L, Cheing G. Efficacy of Biophysical Energies on Healing of Diabetic Skin Wounds in Cell Studies and Animal Experimental Models: A Systematic Review. Int J Mol Sci. 2019;20(2):368. doi:10.3390/ijms20020368

7.        Crowe MJ, Sun Z-P, Battocletti JH, Macias MY, Pintar FA, Maiman DJ. Exposure to pulsed magnetic fields enhances motor recovery in cats after spinal cord injury. Spine (Phila Pa 1976). 2003;28(24):2660-2666. doi:10.1097/01.BRS.0000099385.46102.0D

8.        Inoue N, Ohnishi I, Chen D, Deitz LW, Schwardt JD, Chao EYS. Effect of pulsed electromagnetic fields (PEMF) on late-phase osteotomy gap healing in a canine tibial model. J Orthop Res. 2002;20(5):1106-1114. doi:10.1016/S0736-0266(02)00031-1

9.        Rawe IM, Lowenstein A, Barcelo CR, Genecov DG. Control of Postoperative Pain with a Wearable Continuously Operating Pulsed Radiofrequency Energy Device: A Preliminary Study. Aesthetic Plast Surg. 2012;36(2):458-463. doi:10.1007/s00266-011-9828-3

10.      Ae H, Pilla AA. Effects of Pulsed Electromagnetic Fields on Postoperative Pain: A Double-Blind Randomized Pilot Study in Breast Augmentation Patients. doi:10.1007/s00266-008-9169-z

11.      Cao L-Y, Jiang M-J, Yang S-P, Zhao L, Wang J-M. [Pulsed electromagnetic field therapy for the treatment of knee osteoarthritis: a systematic review]. Zhongguo Gu Shang. 2012;25(5):384-388. http://www.ncbi.nlm.nih.gov/pubmed/22870682. Accessed October 18, 2019.

12.      Chen L, Duan X, Xing F, et al. Effects of pulsed electromagnetic field therapy on pain, stiffness and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. J Rehabil Med. October 2019:0. doi:10.2340/16501977-2613

13.      Ryang We S, Koog YH, Jeong K-I, Wi H. Effects of pulsed electromagnetic field on knee osteoarthritis: a systematic review. Rheumatology. 2013;52(5):815-824. doi:10.1093/rheumatology/kes063

14.      Hulme JM, Welch V, de Bie R, Judd M, Tugwell P, Tugwell P. Electromagnetic fields for the treatment of osteoarthritis. In: Hulme JM, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2002:CD003523. doi:10.1002/14651858.CD003523

15.      Negm A, Lorbergs A, MacIntyre NJ. Efficacy of low frequency pulsed subsensory threshold electrical stimulation vs placebo on pain and physical function in people with knee osteoarthritis: systematic review with meta-analysis. Osteoarthr Cartil. 2013;21(9):1281-1289. doi:10.1016/j.joca.2013.06.015

16.      Bjordal JM, Johnson MI, Lopes-Martins RA, Bogen B, Chow R, Ljunggren AE. Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials. BMC Musculoskelet Disord. 2007;8(1):51. doi:10.1186/1471-2474-8-51

17.      Griffin XL, Costa ML, Parsons N, Smith N. Electromagnetic field stimulation for treating delayed union or non-union of long bone fractures in adults. Cochrane Database Syst Rev. April 2011. doi:10.1002/14651858.CD008471.pub2

18.      Al-Jabri T, Tan JYQ, Tong GY, et al. The role of electrical stimulation in the management of avascular necrosis of the femoral head in adults: a systematic review. BMC Musculoskelet Disord. 2017;18(1):319. doi:10.1186/s12891-017-1663-5

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