Blue Collar Scientist

Hi everyone! My name is Karen, and I’m a veterinarian. I’ve joined this blog to provide a roughly once-weekly column on medicine and related topics. I’m writing under the byline Iatros Iatra Polygenos¹, which in ancient Greek means - as far as we can tell - something like Doctor of Many Species.

A few years ago, I treated a young dog for something - I can’t even remember what now, but I do remember it was a painful condition. While the animal was in the hospital, we gave him carprofen - known commercially as Rimadyl - as well as lots of love. When it was time for the puppy to go home, we sent some carprofen with him, along with the usual instructions about dose. It looked like the puppy was on track for a successful recovery.

Later that night, the unfortunate puppy’s owners decided that the animal was in pain, and that the carprofen wasn’t working. So, without telling me or anyone else at the clinic, they gave the puppy a “natural remedy” - willow bark. Within a couple hours, the puppy was dead.

What happened here?

The post-mortem showed that the poor puppy had extensive internal bleeding and kidney and liver damage. These results strongly suggested the dog died of an overdose of NSAIDs. Carprofen is an NSAID, so I was initially worried that I had made a mistake on the dosage and inadvertently killed the dog through my own error. But when I met with the dog’s owners and had a look at the prescription bottle, the dosage was right. And the owners insisted they had complied with instructions and given the proper dose. A count of the remaining pills showed they were right.

That’s when they mentioned the willow bark they’d given the dog, and it all became clear.

NSAIDs are a class of drugs that reduce pain, inflammation, and fever. They are quite safe, as long as you use an appropriate dosage. But when an overdose occurs, bad things can happen very quickly. If the overdose is minor, the effects can include nausea, vomiting, and ringing of the ears - fairly innocuous. But if the overdose is severe, you can end up with bleeding in the stomach and upper part of the small intestine, dangerously high fever, uncontrollable hyperventilation which leads to a dangerous rise in the pH of the blood, disruption of kidney function, and a loss of the body’s ability to regulate potassium, which leads to loss of muscle control, the stopping of the heart, and eventually death. You can also get cerebral edema - a buildup of fluid in and around the brain - coma, hallucinations, and other not very nice symptoms. It’s important to note that these are the side effects of an aspirin overdose, or a willow bark overdose - they’re both the same type of chemical.

Willow bark was probably the first NSAID. It was first mentioned in the historical record back in the days of Hippocrates. The bark would be mushed up into wine to make a tincture. This potion would cause severe gastrointestinal discomfort, but it would kill pain. The active ingredient in willow bark is salicin, which looks like this:

The molecule is actually very close to that of another NSAID, Aspirin. The resemblance might be more obvious if you mentally rotate the diagram below about 120 degrees clockwise:

Both of these compounds - salicin and aspirin - are metabolized in the body to salicylic acid. Salicylic acid is toxic if there is enough of it around, so if you simultaneously take a safe dosage of aspirin, and a safe dosage of the active ingredient of willow bark, you are going to get more salicylic acid production in the body than the people who wrote the dosage instructions ever intended you to have.

Carprofen is a bit more complex and looks considerably different from aspirin and salicin, but if you look carefully, you can see that one end of the molecule is pretty similar to aspirin:

And indeed, carprofen is also a salicylate drug, just like willow bark and aspirin.

The fascination with natural remedies is causing a lot of problems in people and animals alike. Those who take natural remedies do not always disclose this to their doctor, let alone consult them in advance. This leads to interactions and overdoses that can be fatal. Just because something is “natural” does not mean it is safe!

Another problem is that the FDA does not regulate the manufacturing of natural remedies. Commercially manufactured medication is strictly regulated. The information on a drug’s label - including the amount of active ingredient, and the purity of the preparation - has to be accurate. If it isn’t, it can be recalled, resulting in a sharp financial loss to the manufacturer. In extreme cases, people can go to jail. But with “natural remedies,” the amount of active ingredient is not required to match the manufacturer’s claims, nor are there standards for purity. Depending on the “remedy,” you might be ingesting nothing but fillers from this week’s bottle, and getting more than is safe from the next batch.

Back when I was treating that unfortunate puppy, a lot of resources discussed the hazards of willow bark in terms of potential overdose and interaction with other NSAIDs. Now, there is more research to draw on, and the new information suggests salicin is less toxic and has a smaller chance of leading to upset stomach than aspirin. And it looks like the effects of salicin last longer than aspirin. But there’s bad news - willow bark is not pure salicin; it is also full of tannins, which are toxic and can damage the gastrointestinal tract. White willow bark preparations are between 8% to 20% tannins, but if you are going to get enough salicin for pain relief, tannins are unsafe at around 10%. At most of the measured concentrations, tannins lead to toxicity before a therapeutic dosage of salicin can reached. Tannins can also cause liver and kidney damage, so when they are coupled with drugs that are metabolized by these organs, the result can be deadly.

Based on this new information, I’m no longer so confident that my patient the puppy died of an NSAID overdose, caused by the double-whammy of two different drugs. It could have been a result of kidney damage from tannin toxicity, which made the puppy unable to metabolize the carprofen. Either way, the lesson is clear - NSAIDs, whether natural or medical, need to be treated with respect.

Oh, and one parting thought. I shudder to think about anyone giving an NSAID to a cat. Cats aren’t able to metabolize most NSAIDs, and giving them one could easily kill them, or lead to kidney and liver damage - or at best, just make them extremely sick.

1. I’m aware Iatros is masculine - if a real Greek scholar can help out, I’m all ears. [↩]

The Bad Astronomer recently brought to my attention Jenny McCarthy’s advocacy of using nutritional supplements and dietary restrictions to treat autism. McCarthy has claimed that diet and nutritional supplements help autistic kids, saying:

“I’ve been speaking to moms across the country who are all shouting out the same thing: ‘This (diet and supplement intake) is working.’”

“It’s so heartbreaking to see the medical community not support something called diet and vitamins. And it pains us, city after city after city. I see this heartbreak on these mom’s faces.”

“Autism isn’t covered by [medical] insurance. If things like diets and supplements are working, then why not support it? These kids are getting better and I will not shut up and will not stop fighting about it.”

This parallels a larger set of claims from the DAN and biomedical folks who claim that certain interventions can cure autism. As is well known, Jenny McCarthy and her fellow-travelers are wrong. Diet and supplements don’t cure autism.

There are lots of people who don’t know this, however, and they hear the kinds of crazy things said by McCarthy, the mercury militia, the biomedical quacks, and sundry other nutjobs, and they wonder about this stuff. Occasionally, they ask, well, why couldn’t diet and nutritional supplements help?

When asked, you could trot out the data and go over the statistics. And that would be a great idea in certain situations, such as if you were addressing a conference, or if you were a physician going over the evidence for an interested parent, or if you were a genuine expert blogger who was going over the data for the rest of us.

For the rest of us, though, we encounter these kinds of questions from our acquaintances - those who know we are rational thinkers, who might be under the impression we are knowledgeable or smart, or at least who know we are likely to have an opinion. What’s the best way to respond to these people?

For my part, I admit that diet restriction and vitamin intake could help. Exercise could help. Avoiding sun exposure could help. Wearing special underwear could help. Appealing to a magic sky-god could help.

But then I change the rules of the discussion and take them on a journey through common sense. Here is what I tell them:

The question is whether it is really likely to help.

Let’s have a look at this question rationally. Autism is a neurological disorder caused by disrupted early brain development. Autistic persons’ brains are characterized by differences in size and mass, excess neurons in certain locations, abnormal synapses and dendritic spines, structural differences in mirror neurons, and a differently-functioning cingulate cortex. Genetic differences have been found in autistic persons. The biological evidence suggests the disorder is a result of genetics and environmental interaction during brain development, which results in the fetus “building” a brain which is anatomically and functionally different from that of a typical human.

Now, there are also people who, due to a combination of genetics and environmental influences, develop abnormal hands, feet, palates, noses, kidneys, pancreases, stomaches and other pieces of anatomy.

Do we find those people’s hands/feet/etc attain normality if they consume a specific diet and take vitamin supplements?

No.

As much as it would be nice if nutrients could rebuild a brain into a standard configuration, there’s no reason to think that they could, if they can’t even rebuild other, simpler organs in a similar way.

Another line of evidence makes it unlikely. We do know about thousands of chemicals that can cause the body to reorganize entire organs and body systems into new configurations. Those chemicals are (a) not nutrients, and (b) deadly. The few that aren’t deadly are highly specialized pharmaceuticals that need careful dosing so as to not cause more harm than good - and most of them work despite their tendency to cause organ development to go haywire, not because of it. Potentially, one or a combination of these chemical compounds, if given in the right dosages over a period of time, might possibly result in re-organizing the brain in such a way to ameliorate autism. The problem is, none of these kinds of chemicals are found in any significant amounts in a normal diet, or in supplements.

So the question becomes: why research nutrients? Why think they might work? There’s already tons of evidence that it would be pointless. In the meantime, there are other avenues of research that we have plenty of reason to think could be helpful. Perhaps neurological drugs could result in more-normal brain functioning. Perhaps some kind of surgical intervention could do the same. Perhaps genetic-environmental interaction research could reveal risk factors, resulting in preventive strategies to bar autistic brain development.

All of these techniques have been proven to be effective in other disorders that have origins similar to autism. Whereas nutrition has been proven ineffective in other disorders that have origins similar to autism.

In a world where resources were unlimited, I’d do formal, double-blind, large-n trials of nutrients. In the real world where resources are limited, however, I’m going to spend my money in the place that prior knowledge shows it is most likely to do good. And similarly, I’d be placing my faith in proven or at least plausible treatments, rather than disproven ones that don’t make any sense in the first place.

A study done at Ohio State reveals that aromatherapy might be fun, but it won’t make you well. Researchers there subjected volunteers to two scents - lemon and lavender - or to distilled water over three half-day sessions. They were monitored for heart rate and blood pressure, a skin healing test was conducted, pain reaction was assessed, and psychological tests for mood and stress were conducted, and blood samples were taken.

The blood samples were later analyzed for changes in several distinct biochemical markers that would signal affects on both the immune and endocrine system. Levels of both Interleukin-6 and Interleukin-10 – two cytokines – were checked, as were stress hormones such as cortisol, norepinephrine and other catacholomines.

The results: Neither of the scents had a positive effect on the biochemical markers for stress, pain control, or wound healing; nobody benefitted in terms of heart rate or blood pressure; nobody benefitted from faster skin healing; nobody benefitted from lowered stress; nobody had a boosted immune system; nobody managed pain better.

But a few of the volunteers were in a better mood after being exposed to lemon.

This pretty much lines up with what I’ve thought about aromatherapy for a long time: It isn’t therapeutic. It is just an outgrowth of the potpourri movement, which came from the incense movement that preceded it. Some people find it fun, and if people find aromatherapy scents fun to play around with, that’s good enough for me. But some people think doing something merely because it is fun isn’t good enough, so they had to turn it into a Serious Medical Thing, and/or into a cash cow. Simple as that.

I’m looking forward to Orac’s treatment of the subject - I betcha he can get the paper without forking over $35 to Elsevier for the privilege of reading it.