Botox: The good, the bad and the beautiful

Posted by Samantha Jones, PhD on February 15, 2018 in Drugs, Neuroscience | Leave a comment

Awards season is upon us. From the Golden Globes to the Grammys to the Oscars, we’ve seen celebrities posing on the red carpet, chatting with TV hosts, and accepting awards on stage. All the while I’ve found myself wondering, “Is he happy?” “Is she disappointed?” “Are emotions just out this season?”

The star behind that stoic facade? Botox®, a steadfast red carpet attendee.

Poker Face Guaranteed

Botox Nation, written by sociologist Dana Berkowitz in 2017

Botox is a prescription drug best known for its cosmetic use—reducing the look of fine lines and wrinkles— and is responsible for that emotionless guise, a result of its active ingredient: botulinum toxin. Botulinum toxin is a neurotoxic protein isolated from Clostridium botulinum, a bacterium that can prove fatal when ingested, even in very small amounts.

Botulism

In the early 1800s, German physician Dr. Justinus Kerner was the first to try to understand the action of botulinum toxin. He observed symptoms of what had not yet been coined “botulism” in patients who had eaten spoiled sausages, and deduced that a sausage poison was interfering with the function of their peripheral nervous system. Half a century later, German physician Dr. John Muller coined the illness botulism, on account of “botulus” meaning “sausage” in Latin [1]. In 1949, Dr. Arnold Burgen was the first to conclude that botulinum toxin acts by blocking the communication between your nervous system and your muscles, based on observations in rats whose diaphragms were paralyzed when exposed to the toxin [2].

Hearing the word “Botox” may not put anyone on edge, but mention “botulism” to a doctor and it’s a different story. Guess what? Same bacteria, same toxin, and although relatively rare, botulism is not something to be messed with. Botulism often arises after someone eats food that has been contaminated with C. botulinum, but can also occur in young infants when C. botulinum colonizes their intestinal tract before they’re old enough for their immune system to fight back [1]. Injectable drug use can also lead to botulism when C. botulinum spores enter through the injection site.

The first symptoms of botulism are often facial, as muscles that control the eyes and mouth begin to weaken. If left untreated, muscle weakness spreads to lower parts of the body, soon damaging muscles essential for breathing and proving fatal.

A recent botulism outbreak reported by the Miami Herald

We now know that botulinum toxin works by binding to neurons that produce acetylcholine (ACh). ACh is a neurotransmitter that, under normal circumstances, is released from neurons and then taken up by specialized receptors on muscle cells, causing muscle contraction. Botulinum toxin blocks the release of ACh, stopping nerve to muscle signaling and resulting in paralysis [3]. When Botox is used for cosmetic purposes, a dilute solution of botulinum toxin is injected directly into facial muscles, leading to dramatically decreased muscle movement and, consequently, a reduction in the appearance of lines and wrinkles that would normally form from that movement.

Interestingly, some of the world’s most potent chemical weapons have the opposite mode of action: they increase ACh levels. One of them, nerve agent sarin, inhibits an enzyme that would normally break down Ach. Ach begins to accumulate and overwhelm those previously mentioned receptors on muscle cells, over-stimulating the central nervous system and leading to symptoms that range from vomiting and shortness of breath to (in the absence of an antidote) death.

The Advent of Botox

Source: Botox Cosmetic

Although the history surrounding exactly how Botox came to be is highly contested, botulinum toxin is believed to have first been used in a clinical setting in the early 1970s as a treatment for strabismus, a misalignment of the eyes [4]. Botulinum toxin was shown to weaken the muscles around the eyes, lessening a patient’s “cross-eyed” appearance.

In the late 1980s, ophthalmologist Dr. Jean Carruthers was treating a patient for blepharospasm, a condition signified by a lack of control over eyelid closing, when she discovered that the patient also saw a reduction in wrinkles around the eye. Carruthers injected the facial wrinkles of her receptionist, marking the first aesthetic use of botulinum toxin [4]. I imagine the exchange unfolding like so: “Carol, can you please come here a moment, I want to inject one of the most potent toxins in the world into your face.”

Botox was first approved in 1989 to treat the aforementioned eye disorders, but was officially approved for cosmetic purposes by the FDA on April 15, 2002, marketed as a drug that could improve the appearance of frown lines. Now an enterprise worth almost $3 billion, it has become a societal cosmetic staple: In 2015, of the ~14 million minimally invasive cosmetic procedures in the United States, almost half of them were Botox injections. Botox has been approved for use in 78 countries and, as of 2015, over ten million vials of Botox had been sold in the United States since its approval in 2002.

Botox may be best known for its cosmetic use, but it continues to be employed for a growing number of medical purposes, many of which are not FDA approved.

Not Just For That Silky Smooth Forehead

Do you have excessively sweaty underarms? An overactive bladder? Chronic migraines? Botox may be for you. In these cases, the FDA has approved the use of Botox, but in the case of many other medical conditions where it is currently used, the FDA has not. Botox is now prescribed for a range of conditions, from preventing an abnormal heartbeat during open-heart surgery, to treating cold hands (check out the Cold Hand Clinic at the University of Chicago) to Parkinson’s Disease, a debilitating neurodegenerative disorder that leads to decreased mobility and tremors. In the case of Parkinson’s, Botox is injected into dystonic (spasming) muscles, providing a patient relief as his or her contracting muscles begin to release. Most recently, Botox has been explored as a treatment for erectile dysfunction [5]. Preliminary reports show that Botox injection helps penile smooth muscle tissue relax, allowing for increased blood flow and a successful erection.

Although its use in these non-FDA approved cases is not a question of legality, it’s important to ask: How much do we really know about the systemic, or potentially lasting, effects of Botox? Although Botox is only used to target specific groups of muscles, patients are, don’t forget, playing with a deadly toxin. Although rare, there have been reports of botulinum toxin spreading from the site of injection and causing a variety of side effects, including but not limited to blurred vision and difficulty breathing. Risks are increased in children being treated for vision-related disorders [6]. Children are also at risk when they’re born to parents who start treating them with Botox for cosmetic reasons at a young age (See: true, terrifying story of a pageant mom gone rogue).

So, when you see “derived from sources that exist in nature” on the Botox website, or any other site for that matter, remember that “natural” and “safe” do not necessarily go hand in hand. In the case of Botox, those “natural” sources could kill you. Silver lining: you’ll go out with an incredibly placid forehead.

Literature Cited

1. Azam A, Manchanda S, Thotapalli S, Kotha S. Botox Therapy in Dentistry : A Review. J Int Oral Heal. 2015;7(July):103-105.
2. Burgen ASV, Dickens F, Zatman LJ. The action of botulinum toxin on the neuro‐muscular junction. J Physiol. 1949;109(1-2):10-24.  doi:10.1113/jphysiol.1949.sp004364.
3. Miller J, Clarkson E. Botulinum Toxin Type A. Review and Its Role in the Dental Office. Dent Clin North Am. 2016;60(2):509-521. doi:10.1016/j.cden.2015.11.007.
4. Gart MS, Gutowski KA. Overview of Botulinum Toxins for Aesthetic Uses. Clin Plast Surg. 2016;43(3):459-471. doi:10.1016/j.cps.2016.03.003.
5. Ghanem HM. Re: Botox for Erectile Dysfunction. J Sex Med. 2017;14(6):865. doi:10.1016/j.jsxm.2017.04.662.
6. Dysport (abobotulinumtoxinA) [prescribing information]. Basking Ridge, NJ: Ipsen Biopharmaceuticals; June 2017.

Samantha (Sam) Jones is a science researcher and writer, working toward a PhD in biomedical science at UCSD. Sam grew up in the Boston area as an avid Red Sox fan and lover of lobster, moving west in 2013 to start graduate school. As a graduate student she became increasingly passionate about improving science literacy, which led her to writing for the general public. When not in the lab, or hunched over a computer, you can find her teaching yoga or spending time outside appreciating the beautiful San Diego weather.