PERCEPTION OF A POISON: KEY THINGS YOU SHOULD KNOW ABOUT BOTOX®, ONE OF THE MOST POWERFUL TOXINS KNOWN

There is a potent toxin that is so powerful, one single grain of salt’s worth is enough to kill about 835 average-sized adult humans. And a grain of salt weighs just 0.0000585 grams. The sort of toxin you’d stay away from, right? Wrong! Over five million people a year have this toxin injected into themselves willingly, and pay good money for the privilege. This fascinating substance is, of course, botulinum toxin, commonly known by Allergan’s famous brand, Botox®.  Where does this toxin come from, what is it, and why has it become one of the most studied and effective molecules in medicine?  

Some patients, when they learn that Botox® is actually a poison, understandably get a bit freaked out. The idea of injecting a poison into your body, willingly, doesn’t seem quite right.  But then many substances can be poisonous if consumed in volume.

What about the one that leads to confusion, convulsions, and death.  The stomach swells abnormally and feels like it’s going to tear at the seams. Disorientation and headache slowly set in.  The kidneys begin to fail and the brain swells.  As toxicity increases, the brain squeezes against the skull box, you start to vomit, after which collapse and seizures are inevitable.  The normal balance of electrolytes in cells is tipped and organ failure leads to death.  The deadly substance:  anthrax? VX nerve gas?  Ricin?  No. Nothing like them, in fact.  I’m talking about that stuff you drink every day at the gym, when you wake up in the morning, and when you’re thirsty. These are the symptoms, believe it or not, of water intoxication¹!

You’ve heard the expression, too much of a good thing can kill you.  Well, turns out even water can kill, if you happen to drink litres and litres of it in a short space of time.  Basically, the kidneys can’t keep up and your blood becomes diluted to a level that reduces your blood sodium levels—a metabolic problem termed hyponatraemia².  In reality, water is good for you.  Essential for life, in fact, provided you don’t take a bath and then drink the bath water.  Yuck! So, lets talk about some well-known (and some less well-known) poisons and toxins and one of the most potent of them all that has revolutionised the world of beauty, and is becoming a big hit for its benefits in dermatology, neurology, and even psychiatry. 

GLASS HALF FULL

At a time in the world when whole nations and societies are on tenterhooks, people wait (hopefully at home) for the Covid-19 pandemic to ripple through large swathes of the population.  Some see it as potentially rivalling the Spanish flu pandemic of 1918, or worse.  Others consider it as just another virus that we need to get over and move on.  So people see things differently³.  They always have done, and always will.  Some have successfully cocooned themselves in their habitats, with hoards of supplies and food for sustenance.  Others don’t see the same threat and seem to have barely adjusted their lives at all. 

Anyway, the point is, perceptions differ, and to some people certain viruses, poisons, or toxins are thought of as deadly and things to avoid; to others, they are not feared as much. Although the novel coronavirus that emerged just before 2020 is new to us and we don’t know the full extent of its “virulence”, it seems sensible to base actions, behaviour and acceptance of toxins on fact and evidence. 

A PINCH OF SALT

To find out how toxic a toxin is, scientists often use something called the LD50.  This stands for “Lethal Dose 50%”, or the amount of the toxin that would kill half of a group of animals in an experiment.  Sadly for mice, they are sometimes used to determine LD50—sadly for 50% of them anyway!  Everyone knows cyanide is something that shouldn’t be sprinkled on your steak. That’s because cyanide has a lethal dose 50% (LD50) of just 6mg/kg⁴.  Nothing, though, compared to the tetrodotoxin that kills about fifty Japanese people annually due to poorly prepared pufferfish!  Tetrodotoxin has an LD50 of just 300 micrograms/kg if eaten.  But there’s a cute little frog that lives in Colombia called the Golden Poison Frog that’s skin harbours batrachotoxin, a much, much more deadly toxin. Batrachotoxin the size of two grains of salt is enough to kill you. And there’s no antidote. 

And as I mentioned at the beginning of this article, one single grain of salt’s worth of botulinum toxin is enough to kill about 835 average-sized adult humans. 

“All things are poisons and there is nothing that is harmless, the dose alone makes it so a thing is not a poison” -Paracelsus (1493–1541)

SAUSAGE THERAPY

The botulinum toxin story started in 1820, exactly two hundred years ago, when a German doctor called Justinus Kerner stumbled on a certain sickness. Justinus described nausea, vomiting, fatigue and weakness in the limbs in a group of Germans who were picnicking on sausages.  He called it botulism after the latin “botulus” for sausage.  It took another few decades before the bacteria causing this was identified—that was Clostridium botulinum.  Later again, bacteriologists purified the toxin that came from this bacterial species; the now famous botulinum toxin. Fast-forward to 2020, and the same incredibly powerful toxin has over 25 approved indications in medicine.  It’s injected into children with cerebral palsy, is licensed to treat chronic migraine, reduces problematic sweating, helps treat major depressive disorder, and miraculously irons out wrinkles and lines.  Although it’s the most potent toxin known to man, as the Swiss alchemist Paracelsus put it, “the dose alone makes it so a thing is not a poison”.  Botulinum toxin type A (there are a few types from A to G) injections are the most popular cosmetic procedure in the world—a global industry worth about $7 billion. But there are over 20 other indications for the injections: movement disorders, tremors, spasms in the eyelids, tight muscles, bladder problems, cerebral palsy, migraines⁵.  Studies in dermatology show it helps skin conditions, scars, itch⁶.  Psychiatrists are looking at the benefits in depression and bipolar disorder⁷.  This seems like a lot of conditions requiring a lot of toxin!  Actually less than 1 measly gram of botulinum toxin is enough to treat all of these indications in the entire world.  Now that’s potent!  Before you cancel your anti-aging injection appointment, rest assured the doses used to banish pesky crow’s feet and frown lines are ridiculously small. 

SAFETY IN NUMBERS

As little as 20 paracetamol pills is enough to kill if taken at once. That’s just two or three days worth of paracetamol if you have a headache or flu. Let’s compare that to a lethal dose of wrinkle-reducing botulinum toxin. Given that an average beautifying session of botulinum toxin requires only about 0.00000000005 grams of the purified toxin, you’d have to receive about 21 years worth of injections in one sitting to reach a lethal dose (assuming you are defying aging with sessions four times a year)!  Bottom line: it’s a powerful toxin but is extraordinarily safe when administered in the usual way. Course you have to seek out an experienced aesthetic medical professional to get the look you want and not the wonky eyebrow-look, but that’s a different kettle of fish. 

BRAND AWARENESS

Unless you’ve been living under a rock for the last couple of decades, you’ve most likely heard of the brand Botox®.  There are a bunch of other botulinum toxin type A products, too⁸.  Dysport®, Azzalure®, Xeomin®, Prosigne®, Medytox®, Juveau®.  Having used most of these over the last fifteen years or so, I can confirm they all work pretty well, and all do what it says on the tin. Well, glass vial.  Tinned food can be a source of botulinum toxin-producing bacteria, but that’s the type that goes unchecked and can cause botulism when the bacteria multiply.  There’s a big difference.  We’re not injecting bacteria when we use Botox® or Dysport® or Xeomin® or whatever—we’re just injecting the minisculest (is that word?) amounts of the purified toxin.  So these purified botulinum toxin type A products work by temporarily weakening or paralysing the little muscles of facial expression. 

When the toxin is injected, the nerve cells gobble up the protein (toxin).  The protein then latches onto a receptor called SNAP-25, preventing the chemical message going from the nerve cell to the muscle.  Hey presto!  You get a “flaccid paralysis” of the muscles of the face.  When I say it like that, it sounds like a complication. Let me reword that:  strategic placement of the agent results in chemodenervation and muscle relaxation that smooths overlying wrinkles and rejuvenates, leaving you look refreshed and more beautiful.  There, that’s better.  If you’ve ever had these injections, you might say it’s quick and easy—and it is; but there’s also a certain skill and understanding that’s essential to produce natural, aesthetic results without causing unwanted effects. 

TOXINART

Toxinart is the term used to describe the artistic approach to facial rejuvenation using advanced botulinum toxin type A injections.  I’m just kidding.  I just made it up now; but it is an art as much as it is a science.  Imagine a tug-of-war between two groups, both pulling against eachother. What happens when one of the groups suddenly becomes paralysed?  The other team pull hard without opposition and go hastily in the direction they are tugging.  Now imagine one group of muscles pulling the eyebrows of the face upwards (actually the forehead muscle, frontalis, is the only one pulling the eyebrows up) and another group tugging the brows downwards (the ones are the frown muscles, procerus and corrugators).   Let’s say we inject the frown muscles with a little toxin.  A week or so later and they are paralysed.  The result is the frown lines soften nicely, but also the forehead muscle is now tugging unopposed, so the brows lift upwards.  Bingo—a non-surgical brow lift!  Similarly, if you want to lift the corners of the mouth, experienced injectors will paralyse the little triangular-shaped muscled (depressor anguli oris) that pulls the mouth down, leaving the mouth lifter-upper muscles to work harder and transform a scowl into a smile.  These are just a few examples of the role botulinum toxin can play in facial rejuvenation. 

You might be surprised to learn of the things botulinum toxin can do to enhance your appearance. ‘Upper face wrinkles’ is just the tip of the iceberg.  We use it in the lower eyelid to soften fine lines, in the jaw muscle to reduce square jaw, in the chin, above the lip, for bunny lines, to lift the face (Nefertiti lift), in the turkey neckbands, and in the décolletage. It can be used for a gummy smile, for scars, and to rejuvenate skin when diluted down.  And these are just for cosmesis.  The world of medicine has also embraced botulinum toxin type A as a viable option for treating many conditions. 

WONDERDRUG

With humble beginnings, Oculinum, as it was first known, was first FDA-approved in 1989 for treating cross-eye (strabismus) and spasm of the eyelids.  Later its use in treating movement disorders became apparent: tics, tremors, spasm and contractions in the neck and in limbs of those with cerebral palsy.  Since then, few areas of the body have been spared when it comes to therapeutic injections of botulinum toxin.  Doctors inject this potent “poison” into the eyes, neck, underarms, bladder, vagina, penis, and anus, and for good reason. It’s proven in some cases and being studied in others to treat excessive sweating, overactive bladder, anal fissures, for spasm of the vagina and for premature ejaculation^9,10.  The wonder of botulinum toxin is good reason for being happy, literally; it’s also shown to elevate mood in patients with major depressive disorder. 

So the facts speak for themselves.  Botulinum toxin, despite being a poison of sorts, has myriad benefits.  Are there any downsides? Well, unfortunately the wonderful results of botulinum toxin are only temporary, lasting about 3-4 months for cosmetic indications and a few months longer for medical indications¹¹.  Oh, another downside—it has to be injected so you’ll have to bare a few quick nips. Thankfully it only takes a few seconds and the needle is usually tiny, like a hair.  Speaking of pain, there’s a substance being studied now for use in neuropathic pain and chronic pain¹².  You guessed it—it’s called botulinum toxin! 

References

1. Fatal water intoxication.  Farrell DJ, Bower L. J Clin Pathol. 2003 Oct; 56(10):803-4.
2. Symptomatic hyponatremia after voluntary excessive water ingestion in a patient without psychiatric problems.  Hiramatsu R, Takeshita A, Taguchi M, Takeuchi Y. Endocr J. 2007 Aug;54(4):643-5
3. This is what people really think about the threat of COVID-19 coronavirus. Wood J.  2020 Feb; https://www.weforum.org/agenda/2020/02/coronavirus-covid-19-threat-opinion-poll-public-concern/
4. Handle with care—the world’s five deadliest poisons. Cotton S. 2016 Apr; http://theconversation.com/handle-with-care-the-worlds-five-deadliest-poisons-56089
5. Botulinum toxin: state of the art.  Jankovic J. Mov Disord. 2017 Aug; 32(8):1131-1138
6. Botulinum toxin in the field of dermatology: novel indications. Kim YS, Hong ES, Kim HS. Toxins (Basel). 2017 Dec 16;9(12):403
7. Treatment of major depressive disorder using botulinum toxin A: a 24-week randomized, double-blind, placebo-controlled study.  Magid M, Reichenberg JS, Poth PE, Robertson HT, LaViolette AK, Kruger TH, Wollmer MA. J Clin Psychiatry. 2014 Aug;75(8):837-44
8. Toxins differ according to the serotype, strain of bacteria used, manufacturing and isolation process as well as the complexing proteins associated with the toxin.  Botulinum toxin for glabellar lines: a review of the efficacy and safety of currently available products. Dessy LA, Fallico N, Mazzocchi M, Scuderi N. Am J Clin Dermatol. 2011 Dec 1;12(6):377-88
9. New therapeutic perspectives in premature ejaculation.  Simões Paço J, Jorge Pereira B. Urology. 2016 Feb;88:87-92
10. Optimal dosing of botulinum toxin for treatment of chronic anal fissure: A systematic review and meta-analysis. Lin JX, Krishna S, Su'a B, Hill AG.Dis Colon Rectum. 2016 Sep;59(9):886-94
11. Lasts about 3-4 months but factors that can influence that include dose, sex, formulation, frequency of treatment, and severity of wrinkles.  Botulinum toxin: examining duration of effect in facial aesthetic applications. Flynn TC. Am J Clin Dermatol. 2010;11(3):183-99
12.  Botulinum toxin treatment of pain syndromes -an evidence based review.  Safarpour Y, Jabbari B. Toxicon. 2018 Jun 1;147:120-128