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EVIDENCE UPDATE: A SYSTEMATIC REVIEW OF STUDIES EVALUATING VEGAN DIETS FOR DOGS
AND CATS

Posted on May 11, 2024 by skeptvet

Over the years, I have reviewed the general evidence and some specific
studies concerning vegetarian and vegan diets for dogs and cats. Despite the
aggressive claims of some advocates for such diets (including some egregiously
unscrupulous individuals), the actual evidence has not been extensive or
definitive. My conclusions in previous posts have been that there is no clear
evidence vegetarian or vegan diets have benefits for dogs and cats, and there is
some real potential for harm, especially in cats:

Vegetarian Diets for Dogs & Cats, 2019

> There is no evidence that vegetarian diets have health benefits for dogs and
> cats, and no real reason to believe they should be, based on the physiology
> and nutritional requirements of these species. 
> 
> Dogs are omnivores shaped by domestication to be able to eat both plant and
> animal foods, and in theory they should be able to thrive on vegetarian or
> vegan diets. However, these diets must be carefully formulated, and many
> commercial vegetarian dog foods do not appear to be nutritionally adequate.
> There is also little reliable research evidence showing that dogs can remain
> healthy fed only a vegan diet.
> 
> Cats are clearly obligate carnivores with nutritional requirements that are
> unlikely to be effectively met by vegan diets. Such diets offer only risks and
> no benefits for cats and should be avoided.

Plant-based vs Meat-based Diets for Cats: Which is Healthier?, 2021

> This study didn’t actually evaluate the effect of plant-based vs. meat-based
> diets on health or longevity in cats. What the study evaluated was the
> perceptions of owners about their cats’ diet and health. The difference is
> crucial. 
> 
> All we can say is that owners who choose to feed a plant-based diet believe
> their cats are a healthier weight than owners who feed meat-based diets. Since
> plant-based diets are fed to a small minority of cats, the people who feed
> these diets must choose to do so based on pre-existing beliefs about their
> health value. Such individuals already believe these diets are healthier, and
> they are likely to see and report what is consistent with these beliefs,
> whether or not it is the reality of their cats’ condition.
> 
> Prospective, blinded, randomized feeding studies would be needed to allow any
> strong conclusions about whether or not plant-based diets are safe and healthy
> for cats.

Are Vegan Diets Healthier for Dogs & Cats?, 2022

> The particular population of pet owners surveyed believes that feeding raw and
> plant-based diets are associated with better health in their pets. They also
> believe that their veterinarians think their pets are healthier (though
> whether these vets actually believe this is unknown)…Like previous
> studies relying on owner surveys and both conducted and funded by folks with
> strong a priori opinions about diet and health, this is a useful insight into
> such beliefs. It is not compelling or probative evidence for actual health
> effects of different feeding strategies. 
> 
> Controlled studies with objective measures of outcome and more defined and
> verified feeding practices are required to draw any meaningful, actionable
> conclusions about the healthiest feeding strategy for our pets. 
> 
> I am neither for nor against vegan diets for dogs, and I am even open to
> reversing my objection to feeding vegan to cats or raw diets to cats or dogs
> if strong evidence is generated that these are safe or beneficial practices. 

I recently came across a systematic review of the literature that summarizes and
assesses the available evidence concerning vegan diets for dogs and cats.

Domínguez-Oliva A, Mota-Rojas D, Semendric I, Whittaker AL. The Impact of Vegan
Diets on Indicators of Health in Dogs and Cats: A Systematic Review. Veterinary
Sciences. 2023; 10(1):52. 

The data from review largely support my concerns about the lack of evidence,
though the authors draw a somewhat more optimistic conclusion than I would:

> In this review, we conducted a formal assessment of the evidence in the form
> of a systematic review. We found that there has been limited scientific study
> on the impact of vegan diets on cat and dog health. In addition, the studies
> that have been conducted tended to employ small sample sizes, with study
> designs which are considered less reliable in evidence-based practice. Whilst
> there have been several survey studies with larger sample sizes, these types
> of studies can be subject to selection bias based on the disposition of the
> respondents towards alternative diets, or since answers may relate to
> subjective concepts such as body condition. However, there is little evidence
> of adverse effects arising in dogs and cats on vegan diets. In addition, some
> of the evidence on adverse health impacts is contradicted in other studies.
> Additionally, there is some evidence of benefits, particularly arising from
> guardians’ perceptions of the diets. Given the lack of large population-based
> studies, a cautious approach is recommended.

The short version of this is that there aren’t many studies, and most have
serious flaws or limitations, so strong conclusions either way aren’t justified.

No obviously horrible risks have shown up, but given that the studies which
looked at actual health outcomes were few, short-term, and involved small
numbers of animals on several very different diets, it would be a mistake to
draw the general conclusion that vegan diets are safe.

Similarly, a few studies claim to show health benefits, but these are all based
on owner surveys with groups of owners self-selected to include people already
convinced that vegan diets are healthier. This kind of evidence, also frequently
cited to support health claims for raw diets, is highly biased and tells us more
about what believers in such diets expect to see than about the actual health
effects on their pets.

Finally, some nutritionists have pointed out a significant problem with this
kind of review– the idea that broad categories of diets (e.g. canned, kibble,
raw, fresh, vegan, etc.) can be identified as beneficial or harmful doesn’t
really make sense. The health impact of a diet depends on the specific
composition, the ratio and availability of nutrients in the diet, and the
nutritional needs of each individual. Vague generalizations, such as “vegan
diets are healthy” or “kibble is unhealthy” are so broad as to be pretty
meaningless, and they don’t help us decide what the best diet is for our
specific pets. While some level of generalization is, of course, necessary and
useful, these characterizations go too far to be accurate or helpful.

Bottom Line
There is very little research examining the health effects of vegetarian or
vegan diets in dogs and cats. The existing evidence has significant limitations,
which makes any firm conclusions impossible. 

General theoretical arguments for why such diets should be healthy are not
especially plausible nor convincing. It is likely that a properly formulated
vegan diet could be adequate for many dogs, and possible for cats as well, but
whether there are any benefits to feeding such diets, and whether these might
outweigh potential risks, is not yet known. 

Given this uncertainty, and the much better evidence for the appropriateness of
cooked, meat-based diets, feeding dogs and cats a specific vegan diet is
essentially a haphazard experiment, with as much or more potential for harm as
for benefit.  

Posted in Nutrition | Leave a comment


TALKS FROM WVC 2024- NUTRITION FOR LIFESPAN EXTENSION AND FRAILTY

Posted on April 4, 2024 by skeptvet

Here are some low-quality recordings of a couple lectures I gave this year at
the Western Veterinary Conference in Las Vegas.





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


EVIDENCE UPDATE: IS SURGERY NECESSARY FOR DOGS WITH CRANIAL CRUCIATE LIGAMENT
RUPTURE?

Posted on March 31, 2024 by skeptvet

Back in 2011, I first wrote about the issue of concerning whether dogs with
cranial cruciate ligament (CCL) ruptures did better with surgery or with
non-surgical management. My conclusion at that time was:

> For most dogs under 15kg, conservative management (primarily restricted
> activity for 3-6 weeks, achieving and maintaining and appropriate body weight,
> and possibly physical therapy and pain medication) can achieve acceptable
> comfort and function. In larger dogs, significant arthritis is inevitable and
> dysfunction is extremely likely without surgical treatment. 

In 2013, I write an update looking at an additional study , and concluded:

> This study does provide some support for the contention that overweight,
> large-breed or giant-breed dogs have better long-term outcomes when treated
> with both surgery and non-surgical therapy rather than with non-surgical
> therapy alone. However, the limitations in these data are great enough that
> the case for preferring surgical intervention is not strong

Since that time, there has been some further research, but there has not been
one single, definitive clinical study comparing surgery with other approaches
for managing CCL disease. This is partly for ethical reasons. Since most vets
believe surgery produces a better outcome, it is considered unethical to
randomly assign dogs with CCL disease to getting surgery or getting a
potentially inferior treatment. 

A new study has attempted to use existing data on a large number of dogs, and
some complex analytic techniques, to mimic such a study.

Camilla Pegram, Karla Diaz-Ordaz, Dave C. Brodbelt, Yu-Mei Chang, Anna Frykfors
von Hekkel, Chieh-Hsi Wu, David B. Church, Dan G. O’Neill. Target Trial
Emulation: Does surgical versus non-surgical management of cranial cruciate
ligament rupture in dogs cause different outcomes? Preventive Veterinary
Medicine. 2024; 226;106165.

I don’t have the expertise to evaluate the analytic approach in this study. The
authors acknowledge many of the usual limitations to large retrospective
analyses, but despite these issues, such studies are valuable, especially I the
evidence-poor environment of veterinary medicine. 

The results are pretty consistent in showing better outcomes in dogs treated
surgically:

> The current study shows that on average, surgical management leads to reduced
> lameness and analgesic prescription outcomes compared with non-surgical
> management. 

Interestingly, the study did not find any difference between large and small
dogs. Both groups seemed to do better with surgery, which is a different finding
than some previous research. The authors suggest this may be related to limited
numbers of small dogs being treated, since they are less likely to develop CCL
disease, so further work is needed to clarify the impact of size on the choice
of treatment.

While there are always individual factors to integrate into any decision about
the best management for a specific patient, this additional evidence tends to
support the existing view that surgery probably produces better outcomes for
dogs with CCL disease. While this is not the perfect definitive clinical trial,
such a study is unlikely to occur. The evidence that we do have is pretty
consistent, and it supports at least a moderate degree of confidence in
recommending surgery for those patients in whom it is an option and who have no
specific reasons to avoid surgical treatment.

Posted in General, Science-Based Veterinary Medicine | 6 Comments


FICKLE JUSTICE: SOME QUACKS GET PUNISHED, MOST GET AWAY WITH IT

Posted on March 25, 2024 by skeptvet

One of the goals of this blog has always been to warn pet owners about dangers
to their animals: dangerously unreliable ideas and ways of thinking about
science and medicine, dangerous therapies (or at least those not yet proven to
be safe or effective), and dangerous individuals who promote both unscientific
approaches and unproven or unsafe treatments. There is remarkably little
effective regulation and oversight of pet healthcare products, apart from
prescription medications. Unscrupulous sellers of snake oil, including vets, can
often get away with egregiously illegal and dangerous claims and practices.

Despite this, a few of the individuals I have warned pet owners about over the
years have faced at least some legal or regulatory sanctions, though the process
has been slow and has often not impeded their ability to sell their nonsense.
Recently, one particularly bizarre example, Jonathan Nyce, has finally been
sentenced to prison for selling fake cancer treatments for dogs, a decade after
I started  warning people about him. 

This belated but positive outcome seemed like a good prompt for me to revisit
some of the folks I have been writing about for some time who have faced
official sanction for their abuse of science and the public’s trust. While the
outcome in Mr. Nyce’s case is positive, the balance of these cases have not
resulted in effective protection of the public and our pets.

Jonathan Nyce
My first post about Mr. Nyce was in 2014. In it, I looked at his claims for his
supposed miracle cancer cure Tumexal (later renamed Naturasone). The product and
the marketing had many of the hallmarks of quackery, from secret ingredients to
use of testimonials and unpublished, potentially fabricated, test results. Mr.
Nyce had a worrisome background, including previously questionable and
unsuccessful attempts to market a drug for humans and a criminal conviction for
murder, though I made a point of not making my critique of the product or the
claims for it a personal critique of Mr. Nyce, since that is not a reliable way
to judge such claims. 

In 2020, I briefly reported on the criminal charges filed against Mr. Nyce for
his illegal marketing of a fake cancer treatment. Finally, last month, Mr. Nyce
was sentenced to 97 months in prison for his activities, which included bilking
over 900 dog owners of nearly $1,000,000. Who knows how much harm his deception
of well-meaning owners did to the patients themselves? As tempting as it is to
rejoice at a well-deserved sentence, the more important question is whether this
conviction will do anything to stop others from marketing bogus treatments. I
have to admit to not being very optimistic on this point, for reasons which may
be clearer as I review some other examples.

Gloria Dodd
Even before covering Jonathan Nyce’s misdeeds, I wrote about veterinarian Gloria
Dodd in 2011 (not to be confused with Jean Dodds, about whom more later….). Dr.
Dodd was a proponent of a broad array of pseudoscientific nonsense, from auras
and homeopathy to crystal healing and dowsing. She was also a seller of many
alternative remedies that were either entirely useless (e.g. homeopathic) or
untested and based on unscientific principles.

Her practices were determined to cross legal lines more than once. In 2004, the
FDA sent her a warning letter for selling a fake “homeopathic vaccine” for West
Nile virus. That product was still available when I wrote about her in 2011. 

She was also disciplined by the California Veterinary Medical Board for
practices that were blatantly unscientific, “a smoke and mirror power of magic
type of practice,” in the words of the VMB. Her license was suspended for
prescribing treatments for patients she had never seen in person. However, the
courts effectively overturned this ruling, and Dr. Dodds continued to practice
her “magic” for years to come. 

Dr. Dodd passed away in 2013, but her company continued to promote her ideas and
products for several more years. Regardless of how kind and genuine a person Dr.
Dodd may have been, it is tragic that she was able to mislead pet owners about
health and veterinary medicine for decades and sell products that could not have
been beneficial and may well have harmed patients, either directly or by
replacing other, truly effective remedies. The failure of the legal and
regulatory system to protect the public from such practices is disappointing,
though not unusual.

Al Plechner
Dr. Plechner was another California veterinarian with deeply unscientific
ideas about science and medicine. For decades, he treated patients for the
mythical entity of “Plechner Syndrome” with high doses of steroids, thyroid
hormones, Montmorillonite clay, and a variety of other nonsensical nostrums.
While he claimed to have “research” to back his theories, he never published
anything, and his descriptions sounded like nothing more than anecdotal case
reports. Certainly, he never produced any evidence that convinced actual exerts
in veterinary endocrinology that Plechner syndrome existed or had the causes and
treatments he championed.

Like most purveyors of pseudoscience, Dr. Plechner did have
dedicated supporters, who came out enthusiastically to “correct” me after my
first post discussing his methods. His detractors, sadly, were less willing to
go public. The private veterinary discussion boards on the Veterinary
Information Network (VIN) contain many complaints and laments about Dr.
Plechner’s ridiculous ideas, and about patients inappropriately treated with
unsafe methods, but these never reached the public. 

In 2015, I was contacted by an individual whose cat had been treated by Dr.
Plechner with blatantly inappropriate doses of steroids. The cate suffered skin
fragility syndrome (similar to this case) and faced surgery and a prolonged
recovery from the effects of the drugs. Though several vets saw this cat and
explained that the drugs were the cause of the problem, the owner had difficulty
getting someone to support her complaint against Dr. Plechner, due to a
combination of personal relationships between him and some of the vets and the
general reluctance of veterinarians to call out even grossly inappropriate
behavior by their colleagues. 

The owner was able to find an internal medicine specialist to support her
complaint to the VMB. Unfortunately, the wheels of justice ground slowly and
started turning too late. Dr. Plechner retired and gave up his license in 2016.
This did not automatically stop the VMB investigation, but Dr. Plechner then
passed away in 2017, and no findings were ever released. However, his website is
still active, his books are still for sale, and other vets (themselves with
legal troubles) continue to promote his approach.

Jean Dodds
Dr. Dodds pops up often on this blog as she is a prominent voice in the
alternative veterinary medicine arena, with lots of dubious ideas and unproven
products and practices. I first mentioned her in 2011, in connection with some
research on an oral health supplement, and I have provided detailed coverage
of her unconvincing work on reduced “doses” of vaccinesfor small dogs
(updated here), her unscientific and misleading writing about nutrigenomics, her
bogus “allergy test” as well as other dubious tests she promotes, and many other
topics. 

Most recently, in 2021 I  briefly discussed the citation against Dr. Dodds from
the California Veterinary Medical Boardfor practicing medicine without a
license, as she has done for many years. The citations was “satisfied” in
August, 2023, presumably meaning she paid the fine and promised not to practice
medicine (though I have not been able to find any no public record of how this
was resolved). Despite this, Dr. Dodds profile, and the activity of her company,
Hemopet (which itself has been fighting with the state over tax obligations)
continue to operate openly and freely. The fact that her medical practice has
been illegal for years does not seem to have lessened her influence or her
business activities in any meaningful way.

Andrew Jones

Dr. Jones did not initially get his own post, but he popped up in passing in
another article I wrote in 2010 as an example of the mania for magical “secrets”
that alternative medicine proponents often claim to have for treating health
problems that science-based medicine can’t cure. Later that year, Dr. Jones
chose to give up his veterinary license rather than stop defaming veterinarians
who practice mainstream medicine as a way of promoting his own alternative
approach. It turned out Dr. Jones’ followers were even more aggressively
supportive of their angry saint than those of Dr. Plechner, and when he rallied
them, they went on the attack against me in all sorts of corners of the
Internet. Several years later, Dr. jones was still perturbed by my criticism,
and his supporters continue to leave comments on the blog more than ten years
after my first article about him.

Of course, the reason for that is that losing his medical license has done
nothing to deter Dr. Jones from selling his bogus “secrets,” and all sorts of
products, online. The snake oil business is still booming, and many of his
customers see him as a martyr rather than someone who couldn’t keep his medical
practice consistent with science and the law. He proudly promotes his book,
“From the #1 bestselling author and former practicing veterinarian,Andrew Jones
DVM.” Bizarre! And while some do continue to push back against his
pseudoscientific claims, Dr. Jones has a thriving career selling nonsense and
lies despite no longer being licensed to practice medicine.

Eric Weisman
I first wrote about Mr. Weisman in 2009, the first year of this blog. His ideas
about health and nutrition were bizarre and laden with extremist conspiracy
theories, and his claims about the diets and practices he recommended were
unscientific nonsense. He ultimately lost his chiropractic license and was
sanctioned for practicing veterinary medicine without a license long before I
started examining his claims. In 2011 he faced criminal charges for practicing
human and animal medicine without a license and for animal cruelty. He reached a
plea deal and got a slap on the wrist in 2012 despite his ling history of
illegal and dangerously delusional behavior. 

In 2018, he signed a stipulation from the Minnesota State Dept. of Public
Health admitting to unlicensed practice of alternative medicine and
misrepresenting his credentials and promising not to do it again. He also paid a
$263 fine. In the most bizarre legal resolution to any of these cases I have yet
seen, doing this apparently allows Mr. Weisman to do whatever bizarre voodoo he
likes with the permission of the Minnesota state government:

It turns out that the government of Minnesota has entirely given up any pretense
of protecting the public from charlatans and witchcraft. Mr. Weisman is doing
just as he pleases, offering “consultations:” as well as selling vegan pet food
with longevity claims based on a grossly misleading and unscientific
interpretation of some published owner survey reports.

Apparently, claiming to be able to treat serious life-threatening illnesses,
interpret clinical lab tests and MRI images, and discouraging patients from
seeing legitimate, science-based medical practitioners is now A-OK in Minnesota!
Yet another quack thriving by deceiving the public. 

Posted in Law, Regulation, and Politics | 3 Comments


EVIDENCE UPDATE: LEAP YEARS ANTI-AGING SUPPLEMENT STUDY

Posted on February 29, 2024 by skeptvet

Back in January of 2023 I reviewed claims for a purported anti-aging supplement
for dogs called Leap Years. My conclusion at the time was-

> Leap Years is similar to most veterinary supplements on the market: It is
> based on some plausible ideas with limited supporting evidence, and it is
> marketed with claims that go well beyond anything scientifically proven or
> reasonable. 

In that review, I pointed out that one piece of evidence the manufacturer cited
to support their claims was an unpublished clinical study conducted at the
veterinary school at North Carolina State University (NCSU). That study is still
has not been published in a peer-reviewed journal, but the company has
recently released a report on the preprint service Bioarxiv. 

This is an increasingly common practice which is supposedly intended to make
important information available more quickly, but which in most cases has more
public relations value than scientific value. Until a paper is put through
peer-review, it has only been critically evaluated by the authors or people they
have chosen, which leaves lots of opportunity for bias. Such preprints may
change significantly before publication or even never be peer-reviewed and
published at all. 

Preprints are clearly a lower level of evidence than full published research
reports, but they do at least provide more detail for anyone interested in
evaluating the research and claims made using it. As you have probably already
guessed, that’s what I intend to do here! 

The Study
The study was a blinded, randomized, placebo-controlled clinical trial conducted
in accordance with appropriate methodological guidelines, which is always nice
to see. The authors do a good job of describing the methods, including the
bias-control practices, progress of subjects through the trial, and the
potential limitations. The one critical piece of information missing is the
actual chemical compounds used in the supplement. 

As discussed in my previous review, Leap Years supposedly contains an NAD+
booster, which the company states is not NMN but otherwise does not identify.
This was given daily for the duration of the 6-month study period. The
supplement is also claimed to contain a senolytic, which is also not identified
and which was given on two consecutive days each month during the study.

The FDA is pretty clear that veterinary supplements are not covered under the
limited regulatory rules for human supplements (the Dietary Supplement Health
and Education Act or DSHEA). Anything marketed for animals must either be a food
or a drug. Leap Years is clearly not a food, and the claims made for it very
much sound like treatment claims for a veterinary drugs: 

> [Leap years] significantly improves owner-assessed cognitive function and may
> have broader effects on frailty, activity and happiness as reported by owners.

That would make it seem like the company is marketing an unlicensed veterinary
drug without first demonstrating safety and efficacy, as is required. However,
the FDA does not seem to have the resources or political backing to effectively
enforce these rules, and the same is true for many other veterinary supplements.
Legal or not, it seems to me unethical (if not unusual) to market a supplement
with undisclosed ingredients and claim that it prevents or treats serious health
problems in dogs. This study does nothing to address that concern.

The trial started with 67 dogs randomized to placebo, low-dose supplement, and
high-dose supplement (though the authors refer to these as “low-dose” and
“full-dose,” which seems an obvious attempt to avoid the potential negative
connotations and anxiety that might come with claiming to provide a “high” dose
of whatever the undisclosed ingredients are). Subjects dropped out at various
stages of the study for a variety of reasons. The total dropout rate was a bit
high (19-26% from baseline to final analysis of the data), as is to be expected
with an already old population. However, the dropouts seemed roughly balanced
across groups, so while this might have affected the statistical power of the
study, it probably didn’t bias the results for or against any of the treatments.

The dogs were included in the study if they were at least 10 years old and had
mild or moderate cognitive dysfunction as assessed by a validated tool (CADES).
They also had to be cooperative for behavioral testing and not so sick or
debilitated that they couldn’t complete the various evaluations of the length of
the study. All of these are reasonable inclusion criteria.

There were quite a few outcomes measured, though at least these were
appropriately identified as a primary outcome (which is all that is supposed to
matter when one critically evaluates a study like this) and secondary outcomes
(which are supposed to be viewed as potentially interesting but not probative). 

The primary outcome was the change at 3 months in a validated measure of canine
cognitive dysfunction (CCDR, not the same as used to test dogs for inclusion in
the study). As the figure below shows, all groups improved, including those
taking a placebo, which is a classic finding for non-specific effects of
participating in a clinical study. Patients tend to get better due, most likely,
to the increased care, attention, and monitoring they get as study subjects,
even if the treatment doesn’t do anything (which is part of why having a placebo
group is so important). 

At 3 months, the placebo group looks better than the low-dose group, and the
high-dose group looks better than both, and the authors report, “There was a
significant difference between treatment groups over the three-month period
(p=0.02).” However, differences in “successes” and “failures” (improvement or
worsening of CCDR scores) between groups were not significant at 3 months.

More importantly, it’s not clear if these differences would be meaningful in
terms of function or quality of life even if they were statistically
significant. It is not even clear that these differences are real since they are
variable across time periods and do not show the expected relationship between
dose and response (the placebo group should stay the same or get worse, the
low-dose group should get a little better, and the full-dose group should
improve more than the low-dose group).

Expanding the chart to include the data from the 6-month timepoints (reported in
the supplement to the preprint) shows the lack of these relationships and
suggests that there is not clear and meaningful improvement with the supplement.
Even though the 3-month timepoints was reported as a prespecified endpoint, it
is interesting that it is the only timepoints that seems to show a significant
improvement in a treated group and not the placebo group. Despite the
statistical difference reported, it is pretty clear that the primary endpoint
did not show the treatment to be effective. 

The secondary outcomes also failed to show any clear evidence of a beneficial
effect:

 * The CCDR was measured again at 6 months, and there were not changes nor
   differences within or between the groups

 * There was no change within groups nor differences between them in activity
   level determined by an objective monitoring device

 * There were no significant differences between the groups in the number of
   dogs reported to have maintained the same level of activity. The results also
   don’t show the kind of progressive effect with increasing dose that would be
   expected if there was actually a real treatment effect:
   placebo 55% unchanged 
   low dose 62% unchanged 
   high dose 44% unchanged 

 * Similarly, no significant differences or dose response was seen in the
   percentage of dogs reported to have increased their activity level:
   placebo 20% increased
   low dose 10% increased 
   high dose 39% increased

 * There were no statistically significant differences or dose response seen in
   the proportion of dogs with stable or improved frailty scores:
   placebo 55% stable or improved
   low dose 76.2% stable or improved
   high dose 72.2% stable or improved

 * A variety of cognitive function tests were run on the study dogs. These
   haven’t been validated to show changes over time or drug treatment effects,
   though they could potentially be useful for doing so. There were no
   significant differences and no clear sign of a dose response for these tests.
   
   * Cylinder test- all groups improved with no differences between them
   * Detour test- there was a slight decline in the full-dose group, a slight
     improvement in the other groups, and none of these differences were
     significant
   * Sustained gaze test- all groups improved with no differences between them

 * Gait speed- there were no changes nor differences between groups
   
   Only a limited subset of the results was reported for owner-reported
   happiness in the paper, and I have not dug through the full data spreadsheet
   to find the rest, but the most hopeful subset reported by the authors still
   does not show a clear effect.
   
 * At 6 months, there were some differences in the proportion of dogs reported
   to get better on this measure, but these were not statistically significant,
   and again they don’t show a logical dose response:
   placebo 24% better
   low dose 47% better
   high dose 35% better
   
 * At 3 months, there were some differences in the proportion of dogs reported
   to get worse on this measure, but these were not statistically significant:
   placebo 15% worse
   low dose 10% worse
   high dose 0% worse

The authors also monitored for adverse effects and classified these according to
appropriate standards. There were few serious adverse effects observed, and
these were evenly distributed between the groups and did not suggest any
dramatic safety problems with the product.

Bottom Line
This report does not count as a peer-reviewed publication, and it adds only a
little to the evidence already discussed a year ago to support the product
claims. However, the report is useful in that it provides more detail about how
the study was conducted and what the results were. Generally, the study was
designed and reported appropriately, and the level of control, for bias was
pretty good. Unfortunately for the company, the results failed to show
statistically significant or clearly meaningful benefits for treated dogs. 

The discussion and the company website, of course, try to present the findings
in at least a slightly positive light, but the final statement that the product,
“can be used safely to mitigate cognitive decline in senior dogs and might have
broader effects on dog health manifesting as improved happiness and reduced
frailty” is certainly not supported by the actual results reported here. The
best we can say is that there were no apparent signs of significant risk and
there were a few non-significant findings that might turn out to be mildly
beneficial at a low but significant level in a larger study or with different
outcome measures.

This level of evidence is never the definitive word for or against a treatment,
but that this is the best the company can come up with after over a year on the
market is not encouraging. The company makes claims which seem likely to be
prohibited for a veterinary supplement, and they rely on anecdote and
questionable extrapolation from theoretical science and results in other species
to market the product, and the release of this study does nothing to strengthen
their case.



March 12, 2024- Addendum
Today Dr. Nir Barzilai announced that Dr. Sinclair was resigning from the
presidency of the Academy for Health and Lifespan Research. It is nice to see
some consequences for such clear, commercially motivated misuse of science.
Hopefully, this will encourage Dr. Sinclair to focus more on research and less
on selling unproven supplements, for dogs or humans!

Posted in Aging Science, Herbs and Supplements | 12 Comments


SCIENCE, SCIENCE DENIAL, & DRUG DEVELOPMENT- A RESPONSE TO DR. JUDY MORGAN

Posted on January 25, 2024 by skeptvet

As I’ve mentioned previously, in the last four years I have continued my
clinical practice while also working for Loyal, a biotechnology company pursuing
FDA approval of drugs to extend health lifespan in dogs. There is little overlap
between my SkeptVet activities and my work at Loyal, and of course my writing
here doesn’t represent the official position of the company on anything. But I
do like to share here some of the science and publications on aging that I work
on at the company. Sadly, that tends to draw the attention of those irritated by
my advocacy for science-based veterinary medicine. 

Recently, there was a large amount of publicity surrounding a milestone on the
road to potentially getting our first drug approved at Loyal. While this drew
mostly positive interest, I was accosted on the SkeptVet Facebook page by a
follower of the “holistic veterinarian” Dr. Judy Morgan. Dr. Morgan’s fan asked
me to respond to a FB Live video briefly discussing (or “ranting about,” in Dr.
Morgan’s own characterization) the press coverage of Loyal’s work. 

I eventually had to block this fan’s account for personal abuse, and I don’t
generally bother to respond to trolls since their comments are typically
ignorant and disingenuous, and their minds are firmly closed. Dr. Morgan’s fan
wanted to set up a “debate” between us, a common tactic among alternative
medicine advocates that mistakes theatrical performance for substantive
exploration of evidence-based science. As I explained to her on FB, “science
isn’t about public debate or performance, its about evidence. [Dr. Morgan] can
say what she likes, and support it with whatever evidence she has, and I can do
the same, and everyone can evaluate her claims and support for themselves…How we
sound or look on video talking to each other isn’t useful or relevant, it’s just
theater.”

However, there are some pretty significant misconceptions and misrepresentations
of science and the drug approval process generally in Dr. Morgan’s video, and I
thought it might be useful to take the opportunity to respond to those and,
hopefully, give everyone a clearer picture of how those processes work and how
science gives us the best chance at finding therapies that provide meaningful,
beneficial impact on the health and wellbeing of our pets.

What Was the Fuss About?
The announcement and associated publicity concerned something called Reasonable
Expectation of Efficacy (RXE). This is a standard for supporting evidence that
the FDA sets for veterinary drugs as part of the process of pursuing conditional
approval. Since the regulatory system is complex and not something vets or pet
owners often know much about (I certainly didn’t before becoming involved in
this project!), I thought I’d start with a brief outline of how it works. The
official explanation and detains can be found on the FDA web site.

Any medicine intended to treat disease in animals must be approved by the FDA.
This is to ensure that these medicines are both safe and effective. Of course,
as I’ve said many, many times, nothing is ever perfectly safe or always
effective, and medicine is about balancing the benefits of a treatment against
the potential risks, all in the light of the available scientific evidence and
the frustrating, but inevitable, uncertainty about these. Having FDA approval
means that a significant degree of scientific evidence at multiple levels is
available to support the specific claims of safety and efficacy made for a
prescription drug. This is not perfect, but it’s a great deal better than what
is available for treatments that don’t go through this process (including
supplements and nearly all forms of “alternative” medical treatments).

In the case of the typical FDA approval process, the agency requires several
types of supporting evidence for safety and effectiveness. This includes
pre-clinical research, that is studies done in test tubes or lab animals showing
how a drug works and what biological effects it has. Such studies are an
important part of demonstrating what we call “biologic plausibility,” the
existence of an explanation for how something works that is consistent with
established scientific knowledge. 

Therapies such as homeopathy or “energy medicine” (such as Reiki) lack biologic
plausibility because there is no scientific rationale for how they might work;
they can only work if much of what we know about basic physical, chemistry, and
biology is wrong. While scientific knowledge isn’t always completely correct,
the basic knowledge that is the foundation for most of the successful medicine
and technology in use today is pretty unlikely to be completely wrong. Clinical
studies of these implausible therapies don’t make much sense and are often
misleading.

Once there is good evidence for the underlying biology of how a drug might work,
then a company seeking approval has to test it directly in the species it is
intended for. If the drug is being developed for dogs, then studies must be done
in dogs to understand how the drug works and what risks it may have. Sometimes
this involves studies in laboratory dogs, often beagles, but it may also involve
research in companion dogs. These studies have to comply with rigorous
guidelines for methodology and to control various types of bias and error, so
they are usually stronger evidence than studies not performed under such
guidelines.

Finally, if the evidence to this point shows the drug is likely to be safe and
effective for its intended purpose, a clinical trial is performed. This is the
“randomized controlled trial” or RCT that people most often associate with
medical science, even though it is only one part of a much more comprehensive
testing process. In an RCT, ideally some dogs are given the new drug and others
are given a placebo (a “fake” drug which does nothing at all), and everyone
involved is “blinded” so they don’t know which is which. The details vary with
the specific drug being tested, but again the standards for how these RCTs must
be conducted to gain FDA approval are very specific and quite high, so the
results are pretty good quality evidence. 

This process often takes many years and is very expensive to complete. This is a
problem because it makes it harder for veterinarians to get new and properly
tested therapies. The system in most countries, and certainly in the U.S., is
set up so that private companies are responsible for paying the costs of
developing and testing new drugs, and so they aren’t likely to do so unless they
think they can make back the money invested in this. Lots of interesting
political debates could be had over whether a different system would be better,
but that’s beyond the scope of this blog, and frankly nothing about this is
likely to change here any time soon.

The FDA recognizes that vets can’t get many treatments that have met the high
standards of the typical approval process, and so it allows some compromises to
make useful therapies available to vets and their patients. We are, for example,
allowed to use drugs approved for humans “off-label,” meaning in ways they were
not tested and approved for. Many of the treatments vets use have been tested
thoroughly for safety and efficacy in humans but not in dogs or cats. While this
increases the potential risks when we use them in these species, often this is
still better than the alternative of having no treatment for a given problem, or
having treatments that haven’t even been scientifically validated in any
species. 

The FDA also doesn’t regulate some treatments much at all. The rules governing
dietary supplements are especially lax (and violated all the time with little
consequence), so it is much faster and more profitable for companies to make
supplements than develop prescription drugs. Sadly, this has led to a booming
and lucrative industry (highly favored by alternative medicine advocates like
Dr. Morgan) selling products that may be claimed to be safe or effective even
when there is little to no real evidence that these claims are true.

A more recent change in the FDA approval system has been the pathway of
conditional approval. Under this approach, new drugs must meet all the same
requirements for proving safety, manufacturing quality, environmental impacts,
and so on as under full approval. However, if a product is targeting a serious
health problem with no existing effective treatments (which is clearly the case
for aging), and if the RCT needed for full approval is complex and likely to
take a long time (again, this is clearly true for drugs intended to extend
healthy lifespan), then a drug can be made available to vets for use while that
RCT is being conducted. 

In order to do this, the company must provide sufficient evidence that the
product is likely to be effective (aka reasonable expectation of efficacy or
RXE) along with the usual evidence for safety and other components of approval.
Several products have been made available to vets under this pathway, including
medications for heart disease, pancreatitis,anemia, and epilepsy.

The big news in the press that prompted Dr. Morgan’s “rant” on FB was that the
FDA granted this RXE approval for one of Loyal’s products. The support for this
approval included four years of pre-clinical research and 2,300 pages of data
and documentation, so it is a pretty robust standard even prior to the
completion of the final RCT. The product has not yet been approved, and it is
not expected to be available for at least another year even if it eventually
achieves this approval. However, the milestone was pretty significant since the
FDA has never before granted RXE status (or approval of any kind) for a drug
intended to treat the mechanisms and consequences of aging. Ultimately, this has
the potential to open up an entire new area of preventative medicine, though
there is a long way yet to go towards this goal.

Who is Judy Morgan?
Dr. Morgan is a self-described “holistic” veterinarian. She was in clinical
practice for many years, and since retiring she has focused exclusively
on selling products, books, and educational courses on her web site as well as a
variety of other educational and advocacy activities. She is quite typical of
the alternative medicine advocates I have written about many times. She promotes
Traditional Chinese Veterinary Medicine (TCVM), homeopathy, raw diets,
innumerable untested supplements, and a wide range of dubious or disproven tests
and treatments. She is also deeply suspicious of science-based veterinary
medicine, condemning conventional diets and ranting about the dangers of
conventional drugs, vaccines, parasite preventatives, and other mainstream
medical tools. 

Her educational courses often touch on longevity and geriatrics, and she clearly
has an interest in these areas. However, her advice is largely unscientific, and
she makes numerous false claims about the “proven” benefits of raw diets, TCVM,
supplements, and so on. Anyone who suggests vets should choose supplements and
foods for maintaining health or treating disease based on supporting “elements”
such as Fire, Wood, and Water, or on “balancing” mystical energies like Yin and
Yang, cannot be taken very seriously when commenting on science and scientific
medicine.

What’s the “Rant” About?
Most of Dr. Morgan’s video has nothing to do with Loyal’s products or the
related media coverage. She spends much of her time talking about the work of a
Japanese scientist on apoptosis inhibitor of macrophages (AIM), a protein
supposedly being developed into a dietary supplement or injectable medicine to
prevent or treat kidney disease and extend lifespan in cats (a set of claims
that are themselves pretty dubious, and which I will try to find the time to
talk about someday). 

Unfortunately, she doesn’t make the transition very clear when she switches from
talking about the Loyal RXE coverage and other subjects, and she repeatedly
talks about a “vaccine” for aging, although neither Loyal nor the Japanese
scientist she discusses are developing a vaccine. This may just be a sloppy
shorthand for anything injectable, or a superficial reading of the media
coverage (one web site does describe the AIM product as a “vaccine,” though the
actual company web site makes it clear that is not what is being developed.)
However, since she does spend a fair bit of her time talking about the dangers
of vaccines (while still claiming to support them), I think this is part of the
obvious effort she is making with this video to cast these products in a
suspicious light for her viewers, many of whom are likely as distrustful of
vaccines as she is.

Dr. Morgan begins the video by suggesting that she isn’t impressed by the RXE
approval and she is “gonna wait ten years and see what the reports are” before
even considering using this or any other drug treatment for aging. This is part
of a consistent theme throughout the video– suspicion of scientific evidence and
a preference for anecdotes to evaluate medical treatments. At one point, she
actually says, “one of the great ways to find out what side-effects can be seen
is social media.” ???? In her view, “if people are reporting the same
side-effect time after time after time” then this is a reliable indicator of the
safety of a drug. This ignores the well-established unreliability of anecdotal
evidence (as the saying goes, the plural of ‘anecdote’ is not ‘data’). 

She clearly doesn’t understand the role of pre-clinical evidence, not only
because she recommends therapies that fail to show basic biologic plausibility,
but because she acts as if any use of a drug without a comprehensive RCT is a
dangerous experiment. With regard to conditionally approved drugs, she says,
“When you go to your vet the day this thing hits the market, your dog is part of
that clinical trial, you are saying, Yes, I am going to let my dog be part of
that science experiment…it might have some serious side-effects that we don’t
know about.”

One could claim that she is simply demanding the highest form of evidence for
medical treatments, except that clearly she is comfortable using supplements,
diets, and alternative therapies that have never been shown to be safe or
effective through clinical trials. What is more, she explicitly admits she would
never participate in a clinical trial because she thinks they are too dangerous:
“I will not sign my dogs up for clinical trials. I know somebody has to
somewhere but it’s not gonna be me.” Instead, she has the bizarre but common
belief that scientific evidence is unreliable but if we have enough anecdotes
then we can know what therapies are safe or effective. That is the sort of
fundamental misunderstanding underlies so much of alternative medicine, and it
makes her judgements on specific interventions unreliable.

Consistent with this approach, she often makes false claims about the risks of
lack of efficacy of treatments based on anecdotal reports collected online. For
example, she claims that isoxzoline parasite preventatives “have killed hundreds
of thousands of animals” based on such reports, which is a demonstrably untrue
exaggeration (e.g. 1, 2, 3). She also argues that the allergy treatment
lokivetmab (a.k.a. Cytopoint) commonly ceases to work because of anti-drug
antibody formation (for which there is no substantive evidence) and that there
are “tons of side-effects” but the company “[doesn’t] have to report the
side-effects that are seen once the drug is used widely,” which is
again completely untrue.

Bottom Line
None of the drugs Loyal is developing have been approved for use by the FDA, so
of course no one is claiming they have been proven to be safe and effective yet.
Having strong scientific evidence at all levels is the whole purpose of going
through the prescription drug approval process rather than just launching a
longevity supplement, which is a much faster and easier way to get a product to
market with minimal scientific evidence. More evidence is needed, and it is
being generated.

However, it is clear that better scientific evidence is not really what Dr.
Morgan is concerned about. She already believes she can extend lifespan and
healthspan with therapies that don’t have any meaningful scientific support,
such as raw diets, supplements, and TCVM. And she repeatedly rejects the
evidence when it is favorable to treatments she believes are dangerous base don
anecdote or just simple prejudice against “injections” and “chemicals” and so
on. 

Hopefully, veterinarians and dog owners with a genuine interest in aging and in
prolonging healthy lifespan will be interested in any new tools that are
developed to achieve this. Hopefully they will critically evaluate the strengths
and limitations of the scientific evidence as we all should for all of the
therapies we use. However some, and I suspect Dr. Morgan will be one, will
automatically reject any pharmaceutical as a safe and effective way of extending
healthspan regardless of the evidence because it doesn’t fit their fundamentally
unscientific philosophy. That’s fair enough, of course, but those folks
shouldn’t try to claim that this rejection is really about holding out for more
and better evidence if this is obviously inconsistent with their other claims
and practices.

Posted in General | 4 Comments


AVMA ASKS FOR COMMENTS ON DRAFT CODE OF CONDUCT

Posted on January 6, 2024 by skeptvet

The American Veterinary Medical Association (AVMA) functions mostly as a lobby
and PR organization for veterinarians. It is a membership organization and, as
such, is beholden to whoever its members are, and the organization is very keen
to avoid conflict within the profession or any suggestion of forcing vets to do
anything in particular. The wild political drama surrounding a simple resolution
in the AVMA House of Delegates to acknowledge the demonstrable uselessness of
homeopathy demonstrates this quite starkly.

The AVMA does make some attempts to promote standards “within the family,”
generally in the form of non-binding position statements. These are often pretty
lukewarm compromises between competing interests, but they have some utility.
The AVMA also has a Principles of Veterinary Medical Ethics, and the
organization is currently asking for comments from members on a proposed Code of
Conduct based on these principles.

This document does offer some acknowledgement of the importance of
evidence-based medicine for ethical clinical practice, and it seems possible
that this could be strengthened somewhat, though I am not extremely optimistic.
Nevertheless, I encourage any readers who are AVMA members to participate in
this comment period, and anyone else to consider encouraging any members you
know to do so.


Here is the draft code of conduct.

Here is the comment form.

The commenting period will close at 11:59 p.m. Central Time on March 4, 2024.

Here are the comments I made

Section B
subsection 1
paragraph d

“A veterinarian does not have an ethical obligation to deliver care requested by
a client that they believe would cause unnecessary pain and suffering for the
patient and that is unlikely to be beneficial.”

A veterinarian has an ethical obligation to prioritize offering evidence-based
care that is most likely to be beneficial and that maximizes the ratio of likely
benefit to potential harms.

Recommendation:
I recommend adding the language in bold to this section.

Rationale:
The purpose of a code of conduct is to articulate “specific types of behaviors
that are either expected or required of members of the veterinary profession,”
not merely those behaviors that are not expected. This section indirectly
indicates that veterinarians should prioritize care that is likely to be
beneficial or with likely benefits that outweigh potential harms, yet it does
not clearly articulate a positive expectation for the corresponding behavior.
The section should indicate that the ethical behavior is to prioritize and offer
only care which is expected to have benefits greater than its risks.

Section B
subsection 2
Evidence?based Medicine

“A veterinarian should prioritize the delivery of evidence?based medicine and
should inform the client when a therapy does not meet this standard.”

A veterinarian should eschew practices that do not meet a reasonable standard of
evidence for safety and efficacy.

Recommendation:
I recommend adding the language in bold to this section.

Rationale:
The guidelines recognize that there is an ethical obligation to “prioritize
evidence-based care” because this is the type of car most likely to benefit
patients. If this is true, it is not sufficient to simply inform clients when we
are offering care that does not meet this standard and then offer care that is
not evidence-based or not likely to be safe and effective anyway. Veterinarians
should be expected to eschew practices that are unlikely to have benefits
greater than their risks based on a reasonable standard of evidence.

Posted in General | 4 Comments


WHEN SHOULD A GENERAL PRACTICE VET REFER PATIENTS TO A SPECIALIST?

Posted on January 3, 2024 by skeptvet

General practice veterinarians (GPs) are often faced with the question of which
services they should provide themselves and which should be left to
board-certified specialists. The growing availability of specialty care, the
expectations of many pet owners for advanced care resembling that which they
receive, the expanding availability of new and more technologically
sophisticated interventions, and many other factors all add to the pressure to
limit services in general practice and refer more patients to specialists. 

On the other hand, many pet owners struggle to find and afford veterinary care
of any kind, much less the most advanced. The concept of a spectrum of care has
gained momentum in veterinary medicine largely in acknowledgment of this and in
recognition of the fact that intensive, technologically sophisticated, and
expensive healthcare may not always be available and may not even the best
option for a given patient and client. I was privileged to be invited to
contribute to one of the first attempts to characterize the concept of a
spectrum of care in the veterinary literature, and it has gained significant
momentum since (e.g. 1, 2)

One element to the spectrum-of-care concept is allowing flexibility in what care
is provided and by whom while still providing effective, evidence-based
treatment. General practice vets are very experienced at the art of providing
care within the many constraints of time, money, and expertise available in
private practice.

Unfortunately, sometimes both GPs and specialists, especially some in academic
settings, mistake the most intensive and advanced specialty care for the best
care, or even for the only acceptable kind of care. This makes it harder for GPs
to meet the needs of their patients and clients within the inevitable
limitations of the “real world,” that is, practice outside of universities or
highly affluent communities.

I have been fortunate enough to work for many years at a practice where I was
able to learn and provide advanced care options often considered the exclusive
province of specialists, such as endoscopy, chemotherapy, and ultrasound. While
some specialists have objected to this, many have understood the importance of
avoiding rigid distinctions between primary and specialty care in order to
effectively meet the needs of all our patients and clients.

Recently, I have developed the impression that newer veterinary school graduates
are more reluctant that earlier generations to provide such advanced care tasks.
Whether this is a generational change or a result of the messages they are
receiving in school, such a trend could potentially further limit the
availability of high-quality care and exacerbate both the shortage of veterinary
services and the dissatisfaction driving vets from clinical practice.

I recently wrote an editorial for the Journal of the American Veterinary Medical
Association (JAVMA) intended to explore the issue of specialty referral, and to
hopefully advance discussions within the profession around this subject. This is
based solely on my own experiences in practice, and my understanding of
evidence-based medicine and the spectrum of care concept, so it is only my
thoughts on the subject, not an objective, data-driven analysis. Nevertheless, I
hope this will provide useful context and food for thought to GPs and
specialists, and perhaps to pet owners as well.

McKenzie, BA. Do it yourself or send for help? Considering specialty referral
from a general practitioner perspective. J Amer Vet Med Assoc. 2024; Online
early. doi: 10.2460/javma.23.11.0612

Posted in General, Presentations, Lectures, Publications & Interviews | 3
Comments


EVIDENCE UPDATE: WHAT’S NEW WITH CANNABIS FOR PETS?

Posted on December 19, 2023 by skeptvet

It’s been ten years since my first post on the use of cannabis in dogs and cats.
For a while, I regularly covered new research studies, but the number of those
has become great enough that keeping up with individual papers is not feasible.
Fortunately, the principles of evidence-based have an answer- literature
reviews!

There are two main types of review articles of use to clinicians: narrative
reviews and systematic reviews. Narrative reviews are far more common in
veterinary medicine. These involve individuals or small groups reviewing the
research on a given subject and writing a summary from their perspective. These
reviews can be very useful, and I have written several myself. But of course
they are subject to significant bias. Authors can choose which studies to
include and which to ignore, and they can interpret the results through the lens
of their existing beliefs on the subject. This doesn’t mean narrative reviews
are not useful, but it is a reason for caution in the level of confidence we
place in their conclusions.

Systematic reviews are more formal projects, with clear and explicit standards
to encourage a comprehensive assessment of the research on a given subject and
an objective summary of the strength of the evidence. These are less subject to
bias, but they have the weaknesses of often being inconclusive. When there are
few studies or most research has significant limitations, no confident
conclusion is justified, and most systematic reviews end with the conclusion
that more research is needed. This is especially the case in veterinary
medicine, where having only a few small studies with significant methodological
limitations is the rule.

In the case of veterinary cannabis, there are only a few systematic reviews. One
has looked specifically at the literature for cannabidiol (CBD) use in dogs with
osteoarthritis (OA).

Patikorn C, Nerapusee O, Soontornvipart K, Lawonyawut K, Musikpodok K,
Waleethanaphan K, Anantachoti P. Efficacy and safety of cannabidiol for the
treatment of canine osteoarthritis: a systematic review and meta-analysis of
animal intervention studies. Front Vet Sci. 2023 Sep 15;10:1248417. doi:
10.3389/fvets.2023.1248417. PMID: 37781283; PMCID: PMC10540436.

As expected, this review had to rely on only a few studies (five), and “All
studies were rated as having a high risk of bias.” The conclusion was that CBD
“may reduce pain…but the certainty of evidence was very low.” Fortunately, “CBD
is generally considered safe and well-tolerated in the short-run, with few mild
adverse events observed, such as vomiting and asymptomatic increase in alkaline
phosphatase level.” However, as usual the bottom line is that more and better
research is needed to allow any confident conclusions about the utility of CBD
in arthritis dogs.

A slightly older review looks at all uses of cannabis in dogs.

Lima TM, Santiago NR, Alves ECR, Chaves DSA, Visacri MB. Use of cannabis in the
treatment of animals: a systematic review of randomized clinical trials. Anim
Health Res Rev. 2022 Jun;23(1):25-38. doi: 10.1017/S1466252321000189. Epub 2022
Jun 15. PMID: 35703023.

Only six studies met the criteria for quality to be included, all in dogs “with
osteoarthritis (n = 4), with epilepsy (n = 1), and with behavioral disorders
(n = 1)” and all using CBD as the test treatment. All studies showed improvement
in the conditions being treated, but “studies were heterogeneous and presented
risks of bias that required caution in the interpretation of findings.” As in
the more recent study, “CBD was well tolerated with mild adverse effects,” but
“More RCTs with high quality of evidence are needed, including greater numbers
of animal subjects, additional species, and clear readout measures to confirm
these findings.”  

A few narrative reviews have also appeared in the last couple of years that
provide a good overview of the uses and evidence for cannabis-based remedies in
veterinary medicine. The most comprehensive looks at dogs and cats.

Corsato Alvarenga I, Panickar KS, Hess H, McGrath S. Scientific Validation of
Cannabidiol for Management of Dog and Cat Diseases. Annu Rev Anim Biosci. 2023
Feb 15;11:227-246. doi: 10.1146/annurev-animal-081122-070236. PMID: 36790884.

One interesting lesson from this review is that despite severely limited
evidence and great uncertainty about what cannabis products might be useful for
at what doses with what risks, people are using them all the time for
everything. The perception appears to be that cannabis is a safe and effective
panacea for companion animals, which of course isn’t substantiated by the actual
evidence.

“The cannabidiol (CBD) pet market is expected to increase by $3.05 billion
during 2021–2025, with a compound annual growth forecast to reach nearly 30%…A
survey conducted online in the United States reported that nearly 60% of pet
owners give or were giving CBD to their dogs, and 12% to their cats, most
commonly for treating conditions like osteoarthritis (OA), seizures, cancer, or
anxiety. From these, 64% found it helps with pain reduction, 50% that it aids
with sleep, 49% that it reduces anxiety, and 30% that it reduces convulsions.”

The evidence is generally encouraging for some conditions, particularly pain,
but it certainly is nowhere near the level needed to justify this kind of
confidence among pet owners. Here are some of the main results reviewed for use
of cannabis in various conditions.

 * In canines, recent studies have shown mixed results regarding CBD’s efficacy
   as an adjunct therapy for managing inflammatory conditions like OA. 
 * Mejia et al. found that CBD administered at 2.5 mg/kg twice daily, either in
   conjunction with non-steroidal anti-inflammatory drugs or not, did not
   improve objective measures of pain in client-owned dogs that suffered from OA
   compared to the placebo. The authors found some improvement in both the
   placebo and treatment groups, which was attributed to either caregiver’s
   placebo effect …This was the only study to use objective outcome parameters. 
 * Verrico et al. found a significant reduction in pain (perceived by the owner)
   combined with increased mobility in large dogs with OA when given CBD for 4
   weeks at doses ranging from 0.5 to 1.2 mg/kg. 
 * Similarly, Gamble et al. reported decreased pain and increased activity in
   client-owned dogs administered 2 mg/kg CBD twice daily for 4 weeks. 
 * Brioschi et al. also found that CBD administered for 12 weeks at 2 mg/kg
   twice daily significantly reduced the Pain Severity Score in OA dogs when
   compared to OA dogs not administered CBD. However, all dogs in Brioschi et
   al.’s study and most dogs in Gamble et al.’s study were administered
   anti-inflammatory drugs during the clinical trial, indicating a beneficial
   effect of CBD when combined with anti-inflammatory drugs.
   
 * Whether CBD is effective in reducing epileptic episodes in dogs with IE
   [idiopathic epilepsy]  is inconclusive, and to date there are more clinical
   reports than controlled clinical studies…Two relevant controlled clinical
   trials explored the effect of CBD in dogs with IE…Additional studies are
   needed to strengthen the use of CBD or hemp extract in dogs with IE…Despite
   that, a survey of 297 pet owners with epileptic dogs showed that nearly half
   of these people were using different supplements to help reduce seizures or
   control side effects of other medications, and close to 40% of these
   supplements contained CBD. 
 * A 3-month randomized blinded study found that dogs with IE that received
   whole hemp extract (THC [tetrahydrocannabinol] < 0.3%) infused hemp oil at
   2.5 mg/kg CBD twice daily in conjunction with other epilepsy drugs had a
   reduction of seizure frequency by 33% compared to the control group. Some
   study limitations included the small sample size of dogs who completed the
   trial and the fact that the data could have been analyzed as repeated
   measures over time to detect individual changes.
 * Garcia et al. conducted a double-blinded placebo controlled cross-over
   clinical trial in which dogs with IE received a CBD/CBDA-rich hemp extract at
   an approximate dose of 2 mg/kg twice a day for 3 months, in addition to 3
   other antiepileptic drugs.  
 * Similarly, McGrath et al. found a reduction in the total number of seizures
   (8.0 ± 4.8 placebo versus 5.0 ± 3.6 CBD/CBDA), as well as seizure days (5.8 ±
   3.1 placebo versus 4.1 ± 3.4 CBD/CBDA), when dogs were administered the hemp
   extract. 
   
 * Animal studies on anxiolytic effects of CBD have shown mixed results. CBD
   seems to have a bell-shaped curve for managing anxiety, as it seems to be
   anxiolytic at moderate but not low or high levels…A meta-analysis on human
   studies concluded that the evidence on cannabis-based products’ effects on
   anxiolysis is incomplete, because most studies had a small sample size along
   with some inconsistencies…In dogs, there is no established dose for treating
   anxiety and fear disorders. The few studies available have focused mainly on
   the short-term effects of CBD on aggressiveness and fear.
 * A research study on shelter dogs found that CBD (dose calculated to be ?3.75
   mg/kg) administered to dogs for 45 days could reduce aggressiveness toward
   humans but not behaviors related to stress.
 * A second study assessed the effect of CBD supplementation on reducing acute
   fear triggered by fireworks in dogs supplemented with 1.4 mg/kg/day for 7
   days and found no effect of CBD alone on reducing fear-induced stress. 
 * Although there is a need for more scientific evidence that CBD is a
   therapeutic option to treat behavioral problems in dogs, like fearfulness and
   anxiety, pet owners perceive the calming and antianxiety effects of CBD
   favorably. Approximately half of pet owners who have given CBD to their dogs
   to reduce fear or anxiety think it is effective, even though doses given are
   inconsistent.
   
 * No in vivo studies assess the antitumor effects of CBD in either dogs or
   cats.
 * Several in vitro studies on canine tumor cell lines have demonstrated
   cytotoxic effects of CBD on cancer cells. [However, you can run a study
   showing bleach kills cancer cells in vitro, but that doesn’t make it a safe
   and effective therapy for cancer patients.]

The authors also touch on one of the persistent problems with veterinary
cannabis products– since they are sold over-the-counter with no meaningful
regulation (and often with illegal claims), there is poor quality control. “Some
reports have noted inconsistencies in pet CBD supplements that are available in
the market, such as misleading or untested claims, violations of good
manufacturing practices, lower amounts of CBD than what was stated on the label,
and/or THC above the allowed limit (0.3%). Unfortunately, many cannabis products
are marketed in the United States with unsubstantiated claims of efficacy.”

As with most studies and reviews, the general conclusion is that the safety
profile of non-THC cannabis products is pretty good, though adverse effects do
occur. In dogs, there is great variability in the absorption and blood levels of
CBD and other relevant compounds with different products and forms, so we still
have little idea how much of any given product is safe or useful to give. In
cats, the research is even sparser, and since cats appear to be more sensitive
to the effects of cannabis-derived compounds (as with most other drugs), the
safety and effectiveness of existing products in cats is largely unknown. 

Both dogs and cats have show gastrointestinal symptoms (e.g. vomiting and
diarrhea0 as well as changes in some laboratory values. Lethargy or sedation and
behavioral abnormalities can also occur, especially with products containing
THC. It is also recognized that CBD and other compound sin cannabis can build up
in fat tissues over time, so even when the short-term risks appear to be low,
there is no reliable research identifying what risks might occur with long-term
use.

Another narrative review from 2023 focuses on the specific use of
cannabis-derived chemicals for treatment of pain.

Miranda-Cortés A, Mota-Rojas D, Crosignani-Outeda N, Casas-Alvarado A,
Martínez-Burnes J, Olmos-Hernández A, Mora-Medina P, Verduzco-Mendoza A,
Hernández-Ávalos I. The role of cannabinoids in pain modulation in companion
animals. Front Vet Sci. 2023 Jan 4;9:1050884. doi: 10.3389/fvets.2022.1050884.
PMID: 36686189; PMCID: PMC9848446.

This review mostly addresses the underlying biology of cannabinoids and pain.
The few clinical studies mentioned are mostly in dogs with arthritis, and the
results are mixed, as discussed in more detail in the previous review. The
authors conclude there is some evidence to support use of cannabis-derived
chemicals for treatment of both acute and chronic pain, but the evidence is
largely extrapolation from lab animal studies (especially rodents), and there is
little real-world scientific research in dogs and cats to support this.

Bottom Line

Most other reviews have looked at the same limited set of studies and drawn
similar conclusions. What we can currently say about the use of CBD (virtually
no evidence related to other compounds in cannabis) is this:

 * It is biologically plausible that CBD may be useful in treating pain,
   inflammation, epilepsy, and possibly some behavioral problems in dogs and
   cats.
   
 * The existing evidence is extremely weak. We can have a low degree of
   confidence in the short-term use of CBD for OA pain in dogs. All other uses
   rely on extremely limited, low-quality, and often conflicting evidence.
   
 * The short-term negative effects of CBD, and cannabis generally, appear to be
   mild. The long-term effects are unknown.

Cannabis is the archetype of a “dirty” drug. It contains hundreds of compounds,
most not studied in any depth, and it has effects on many body systems. While
this means there is a great potential for cannabis-derived compounds to be
useful in many different conditions, it also means the potential for unintended
effects and interactions with other drugs is very high unless specific co pounds
or subsets of compounds are studied and used individually.

Proponents often talk about the “entourage effect.” This is an idea common in
herbal medicine that having multiple compounds in a plant-based remedy is a good
thing because they will work in harmony to increase beneficial effects and
cancel out each other’s adverse effects. There is no reliable evidence that this
phenomenon actually occurs, and it is not very biologically plausible. 

The idea originated with the belief that such remedies were purposefully
provided to humans by God, and as such were designed to have this benign
nature.  Only the “unnatural” isolation of individual compounds to use as drugs
is responsible for the phenomenon of drug side-effects. This argument is not
scientifically credible, and it is far more plausible that mixing multiple
compounds leads to more adverse and unintended effects. 

Certainly, this is the case with use of cannabis in dogs and cats when THC and
CBD are both present in significant amounts. Isolating the CBD reduces these
negative effects, so we cannot just assume that using products with multiple
compounds and only the THC removed is inherently better than using purified CBD
or other cannabis chemicals. Such an entourage effect could occur, but there is
not yet compelling evidence for it.

The other important lesson to draw from these recent reviews is that the
popularity of cannabis products for dogs and cats is not based on real
scientific evidence showing these are safe and effective. This is a fad derived
from the popularity of cannabis use in humans, which has origins in ideologies
around “natural” medicine, reactions against excessive and largely irrational
government prohibitions of cannabis, and factors that have little to do with the
actual merits of cannabis as a medicine. 

Hopefully, the high level of interest will drive more research, and we will find
out what uses it has. I am concerned, however, that the great confidence pet
owners already have in cannabis will mean it continues to be profitable to make
and sell unregulated and untested products without any motivation for companies
doing so to produce meaningful scientific research evidence. Like glucosamine,
which has generated billions of dollars for decades despite being almost
certainly useless, the cannabis-based supplement market may be just another
example of companies seeking profit and consumers seeking panaceas with neither
bothering to put in the effort needed to determine what is actually safe and
effective treatment for our pets. 

The evidence has certainly grown in the ten years since I began discussing the
issue. Unfortunately, it is still weak and limited, and the enthusiasm for
cannabis has grown much faster than the scientific evidence.

Posted in Herbs and Supplements | 2 Comments


CAN WE MAKE DOGS LIVE FOREVER?

Posted on December 2, 2023 by skeptvet

No.

Well, that could easily be the shortest SkeptVet blog post ever, but I guess I
can’t really leave it there. For one thing, the answer should really be, “Almost
certainly no,” since my level of confidence is high but not absolute. Secondly,
it’s the wrong question to be asking, and not one in which I have any interest.

The subject has come up because of some recent publicity around my work
with Loyal, a biotechnology company working towards FDA approval for drugs to
extend lifespan (the number of years lived) and, more importantly, healthspan
(the time lived in good health) in dogs. We recently achieved a pretty exciting
milestone on this path, and this has generated a lot of media coverage. 

Unfortunately, media coverage of science generally, and veterinary medicine in
particular, is often fluffy and ebullient but short on details and nuance. I
think a lot of folks may be coming away with the wrong impression about our
goals and our work at the company and about what this recent announcement really
means. Since SkeptVet readers are hardy enough to tolerate more detailed
content, I thought I’d try to set the record a bit straighter here. [Here I will
insert the necessary disclaimer that what follows is my understanding and
opinion, not the official position of the company I work for.]

I’ve written about aging quite a bit here and in the scientific literature, as
well as talking about it for several years at veterinary continuing education
meetings (you can check my latest CV for list). My claims about it are simple
and, I believe, pretty scientifically sound-


 * Aging is not a mysterious inevitability built into the universe–it is just
   biology. Complex biology, but nevertheless a process composed of elements we
   can understand through scientific investigation.

 * With that understanding comes the potential to influence the process in
   beneficial ways, as we do many other pathophysiologic processes in medicine. 

 * Aging may be most usefully thought of as a modifiable risk factor for the
   negative health outcomes often associated with being aged- disability,
   disease, and death.

 * Basic science and pre-clinical animal model research, including a very little
   bit in dogs, supports these claims. The next logical step is to turn this
   knowledge into practical preventative healthcare interventions.

So far, I think, so reasonable. Where thinks get dicey, as always, is what some
folks claim is the potential of such interventions, and the extent to which
specific approaches are or are not yet “proven” to affect aging and health.
Again, my claims here are pretty simple, and I think reasonable-

 * We will likely be able to extend lifespan and significantly delay or reduce
   age-associated disability, disease, and death in pets and in humans.

 * The extent of our ability to accomplish this cannot be accurately predicted
   at this point. It will likely be enough to matter, to be meaningful in
   real-world terms. It will likely not be anything even remotely approaching
   “immortality,” at least in the foreseeable future.
   
 * There are, as of now, no properly validated or “proven” interventions to
   significantly extend lifespan and healthspan in dogs and cats by directly
   targeting aging. The closest we have is the pretty good evidence for the
   health and lifespan benefits of
   
   * Appropriate weight management (dogs, cats)
   * Some elements of regular preventative veterinary care (e.g.)

Even these require further research to validate and clarify the specific
approaches and the effects on lifespan and aging-associated health problems.  

With that as the context, what have we achieved at Loyal and what does it really
mean?

We have chosen to pursue FDA approval for prescription medications, rather than
whipping up an “anti-aging” supplement to sell with minimal oversight and
evidence, because we believe this process better ensures the final product is
safe and effective. FDA approval is a pretty high bar, but it is by no means
requires the highest possible level of evidence. As a refresher, here is the
pyramid of evidence I have harped on for years-

The best evidence for any medical intervention is ultimately a solid foundation
in well-understood basic science (i.e. biologic plausibility) combined with
multiple high-quality clinical trials conducted by multiple investigators with
different biases and agendas. This, sadly, is a level of evidence virtually
never available in veterinary medicine due to the time, expense, and
logistically challenges in producing it. 

The best we can usually hope for is biologic plausibility demonstrated by decent
pre-clinical evidence and then one or two moderate-quality clinical trials with
decent bias-control mechanisms. Even this is more than the vast majority of
therapies in current use in veterinary medicine have, but if we sit on our hands
and wait for perfect evidence, we won’t have any tools to help our patients. 

I have always said that we should choose the best therapy we can based on the
best available evidence. That may be no more than a handful of anecdotes
(sadly), but that can be appropriate if the need is great enough, we give the
client sufficient honest information to understand the risks and uncertainties,
and we proportion our confidence in the treatment to the level of evidence so
that we can abandon treatments that are unsafe or ineffective when new evidence
comes along.

In the case of regular FDA approval, there is a requirement for strong evidence
to support biologic plausibility (a plausible mechanism of action, research
evidence showing the drug is present in the body and acting on the physiologic
pathways it is supposed to act on, etc.), safety (including testing in
individuals of the species the drug will be used on at multiple doses, including
some that are higher than the actually intended clinical dose), appropriate
manufacturing methods, and no significant negative impact on the environment or
human food safety. 

There is also a requirement to prove clinical effectiveness– that the drug
actually does what it is meant to do in animal patients. This last criterion
usually requires a well-designed and properly conducted field trial, meaning a
clinical trial in real-world patients. While this is, again, not the best
evidence one could possibly ask for, it is strong evidence and far better than
most veterinary therapies ever achieve.

The FDA also allows a slightly different pathway for what is called “conditional
approval.” In situations where there is a serious health problem for which no
proven effective treatment exists, a new treatment can sometimes be
conditionally approved to be used in patients before completion of this field
trial. All of the other criteria must still be met as usual, including
demonstration of safety, but effectiveness can be substantiated by showing
“reasonable expectations of effectiveness” through evidence other than a full
clinical field trial. Even this is only allowed if conducting a field trial
would be so complex and time-consuming that it would significantly delay the
availability of the drug to patients who, again, have a serious health problem
with no currently available approved treatments. 

The field trial must still be done, but the drug can be made available
temporarily (for one year at a time up to a total of five years). This is
intended as a compromise between the need for strong evidence to support
efficacy and the need for new treatments to be made available to patients with
serious health problems as quickly as possible.

There are several conditionally approved therapies on the market now, including-

 * Laverdia for treatment of lymphoma
 * Panoquel for pancreatitis
 * Pimobendan for dogs with mitral valve disease
 * Varenzin for cats with anemia due to kidney disease

So what does all of this have to do with our work at Loyal? Well, we recently
received a notice from the FDA indicating that the agency accepted the evidence
we submitted for one of our products, called LOY-001, as sufficient to meet the
standard for a reasonable expectation of efficacy. Let’s start with what
this doesn’t mean-

 * We are not marketing a drug for aging. LOY-001 hasn’t completed the other
   steps in the conditional approval process and is not available for use. If
   all goes well, we may finish this process in 2026, but that is only a goal,
   not a prediction.

 * We are not claiming this or any other product extends lifespan or slows
   aging. The whole point of pursuing FDA approval is that we can’t and won’t
   make any claims about any of our drugs until the FDA says the evidence is
   sufficient to support those claims and grants approval.

 * We are still planning on completing the full approval process for any drug we
   market, so even if we achieve conditional approval for this or another
   product, that doesn’t mean we accept reasonable expectation of efficacy as
   the final standard of evidence. 

 * We’re not claiming, and will never claim, that any drug makes dogs live
   forever. The obsession with immortality is a distraction from the more
   realistic and meaningful work of prolonging healthspan and reducing the
   suffering associated with aging.

With that clarification, I will address some of the questions and concerns I
have heard since the announcement. 

To begin with, some folks feel that the conditional approval pathway is
insufficient to demonstrate effectiveness and that no drug should be used until
it achieves full approval after a field trial. That’s a perfectly reasonable
position, and I won’t try to argue anyone out of it. I will point out, though,
that the purpose of having a conditional approval process is to acknowledge that
delaying the availability of new treatments while a field trial is completed,
especially one that will take a long time, does have a cost as well as a
benefit. While the final evidence is stronger, and while we may be glad we
waited if the field trial doesn’t confirm the expectation of effectiveness,
patients are going without treatment while we wait. 

Aging is arguably responsible for the vast majority of the disability, disease,
and death we see in senior dogs, and there are no approved or well-validated
treatments currently available to target this major cause of suffering, so it
certainly represents an unmet need. The fact that we have always accepted it as
inevitable and immutable doesn’t mean there is no urgency to developing
treatments for it, only that we aren’t yet accustomed to thinking about the
harms of aging the way we think about the harms from cancer, chronic kidney
disease, or other health problems in our pets and patients. 

Obviously, any clinical trial evaluating the effect of a drug on lifespan is
going to be complex and take a long time. We are planning several such trials.
The first, for a different product, is starting this month and will involve
1,000 dogs studied over 4-5 years. This is probably the largest clinical trial
ever done in veterinary medicine, so it certainly counts as complex and
prolonged. A field trial of LOY-001 would likely be very similar.

If LOY-001, or any other drug targeting aging, achieves conditional approval, it
will have met the same standards of evidence for safety as any fully approved
drug. Vets and dog owners will then have to decide whether the potential
benefits outweigh the uncertainties inherent in the reasonable expectation of
effectiveness standard and whether they want to use the drug right away, wait
until a field trial is complete and it is fully approved, wait until the drug
has been in use for some period of time after approval, or whatever other
standard of evidence they feel is appropriate. That is the same decision we all
must make for any new treatment that becomes available, and there is no absolute
or universally “right” or “wrong” choice.

Some readers have expressed concern that I am helping to work towards
conditional approval for this drug while having been critical of other
treatments, both conventional and alternative, based on claims or uses for these
without sufficient evidence. This seems inconsistent to some folks. I don’t
believe that is the case, and I think a close reading of my critiques of many
different therapies will show that I do not argue absolutely against the use of
anything unless there is either clear evidence that the risk outweighs the
benefits. I frequently point out that using even therapies with minimal
supporting evidence is fair if, as I said earlier, the need is sufficient, there
is informed consent, and we don’t make claims with unjustifiable confidence. 

In the case of any conditionally approved product, including those that may
become available from Loyal, I believe the risks and benefits of their use
should be weighed in the context of the uncertainty and claims should be
proportional to the strength of the evidence. If LOY-001 or another Loyal
product becomes available under the conditional approval pathway, I will apply
this same standard. As of now, I am not making any claims since there is no
approved product to make them for.

I have also been asked why, if there is no drug actually available, this
milestone matters at all. The answer to that has to do with the issue of how
aging is approached in veterinary and human medicine. 

We have traditionally played a game of whack-a-mole with age-associated health
problems—waiting for them to appear and then treating them as best we can. Since
aging has been considered inevitable and just a fact of the universe, we haven’t
thought much about it in terms of prevention or of treating the underlying
causal mechanisms of age-associated disease. This has included a reluctance to
consider aging a treatable problem for which drugs could be developed and
approved. The FDA acceptance of our evidence for reasonable expectations of
effectiveness is the first time, as far as we can tell, that the FDA or any
other health regulator has accepted the idea that a treatment could be approved
for extending lifespan or mitigating the consequences of aging by targeting the
mechanisms of aging directly. 

This opens up the possibility of an entire new field of medicine and a
proactive, preventative approach to aging. Whether or not LOY-001 or any other
specific drug achieves approval, this is a significant milestone in the effort
to change how we approach aging and age-associated health problems. For once,
veterinary medicine is leading rather than following human medicine! 

Finally, there is the question of my own bias with regard to this and other
products produced by Loyal because I am an employee of the company. The question
is not whether or not I have a bias, because of course I do! I have a financial
interest in the success of the company, and while I believe my ethics would
prevent me from saying anything misleading or untruthful about the company or
our products, financial bias is a reality, and it is fair to acknowledge the
potential subtle and unconscious influences this may have on anyone.

As I have explained many times before, though, I think the more interesting and
important source of bias is ideological and institutional. I wouldn’t work for
Loyal if I didn’t feel like the values and goals and scientific work being done
there didn’t already align with my own views and values. I tend to agree with
the approach to aging and the way we are going about our work not because I get
paid by the company but because I chose to work for them in the first
place because of this alignment! 

Does that mean anything I say about the company or our products is meaningless
or should be dismissed due to my bias? Well, that’s up to each reader to decide
for themselves. What I will say is that, in an ideal world, no claim about a
medical intervention should ever be accepted entirely on the basis of the
opinions of any individual, including me. We should all review the objective
evidence critically and make our own decisions. If our products achieve
conditional or full approval, the evidence will all be publicly available for
people to use in making up their own minds. 

That said, we can’t all be experts on every subject, and we don’t always have
the time or skills to evaluate every claim effectively on our own. When I have
questions about infectious diseases, I give great weight to the opinions of
trusted experts who I know have an evidence-based approach and the expertise to
make critical judgement about this area (e.g. Dr. Weese). I do the same in other
areas, relying on the expertise of nutritionists (e.g. Dr. Larsen, Dr.
Weeth, Dr. Villaverde), cardiologists (e.g. Dr. Rishniw), and so on. I balance
independent critical thinking with a recognition of the inevitable limitations
of my own knowledge and capacity, and I rely on others to help inform my
understanding of specific topics. 

We all have to do this since we cannot know everything about everything. The
biggest challenge is identifying reliable sources and striking a balance that
doesn’t fall into the traps of overconfident independence on one end or blind
following of equally imperfect humans on the other. How people choose to regard
my opinions and evaluation of any subject, including aging therapies, will be a
decision of this sort.

Posted in Aging Science | 4 Comments
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