Botulinum toxin products, mainly Botox, Dysport and Xeomin, in recent years have gained a great popularity as the best solution for smoothing facial wrinkles caused by excessive activity of the muscles. For example, in 2018, 11.5 million botox injections were performed in the USA alone. Multiple promotional articles written by different authors claim that smoothing wrinkles with a use of botulinum toxin is a quick, safe procedure with a low risk of side effects. Sometimes these authors go as far as to present botox as some kind of non-toxic form of botulinum toxin that has nothing to do with the deadly poison. However, throughout the history of using botox in medicine, there have been reports of serious side effects and even deaths associated with the use of it. So, is botox dangerous? Is botox poison? And what do we know about it at all?
In the 1970s, American ophthalmologist Alan Scott began to experiment on his patients who suffered from blepharospasm (abnormal contraction of the eyelid muscles), by injecting an unusual medicine based on botulinum toxin, the most powerful natural poison that causes a deadly form of food poisoning – botulism.
The first symptoms of botulism were described in the XIX century. The main feature of this disease is progressive paralysis, which in most cases leads to death as a result of respiratory failure. Since the poisoning was mostly occurring after consumption of sausages contaminated with a bacteria that produces this toxin, it was named “Botulinum Toxin” (which means “sausage poison” – botulus in Latin means “sausage”) while the poisoning itself was named “Botulism”.
Although botulinum toxin is certainly dangerous, there was nothing unexpected in Scott’s ideas, because much earlier, in the 1950s, scientists found that a purified and highly diluted toxin could be used, albeit with a great care, for medical purposes to relax muscle spasms. Soon, seeing a high percentage of cured patients, other doctors followed Scott’s example and started gradually expand areas of toxin use. In particular, botulinum toxin was used to treat Strabismus and Hemispasm (spasm of one half of the face). Even then some doctors, who were treating patients with botulinum toxin, noticed an interesting side effect: in the areas of injections such wrinkles as frown lines between the eyebrows and folds in the corners of the mouth were miraculously disappearing. The patient, therefore, was not only getting rid of the annoying spasm, but was also gaining a youthful, relaxed and friendly facial expression. Soon, many emergency rooms of the neuropathologists started getting an unusual kind of patients: well-to-do women in their 50s who were willing to risk everything in order to look younger.
Today, the science is familiar with several types of botulinum toxin that differ in their immunological and chemical properties. The first commercial product containing botulinum toxin was Botox: for its creation, the manufacturer has chosen botulinum toxin type A (all types of toxin are in Latin letters), which for a long time remained the only type of botulinum toxin used in medicine. However, recently a few products containing another type of botulinum toxin – type B – became commercially available. They are known as brand names Neurobloc and Myobloc. All the other types of botulinum toxin currently are not used in medicine.
In 1989, the FDA approved the use of Botox for treatment of several diseases related to involuntary muscle contractions. And although the wrinkles were not listed among Botox’s indications, more and more doctors began to use it “off label” (not for its intended purpose).
Only in 2002, the FDA finally approved the use of Botox for cosmetic purposes, to be exact, for elimination of facial wrinkles on the forehead and around the eyes. From that moment on, Botox began its triumphal ascent to the pinnacle of success.
DIFFERENT TYPES OF WRINKLES
Now let’s talk about where the wrinkles come from and why they disappear after injections of botox.
Wrinkles that cause us so much distress, not only look different, but have different causes. Many wrinkles form as a result of general aging and changes within the skin that take place as we age. All you’ve heard about collagen destruction and the damage done by the UV radiation and other harmful factors, refers to this type of wrinkles. But there are other wrinkles, which represent folds of skin that form at the site of the usual spasm of the muscles. When contracted, the muscle shortens and wrinkles the skin, and when relaxed, the muscle returns to its original position and “pulls” the skin back. In young people, skin has a great elasticity which helps to quickly react to such muscle movements and just as quickly get restored. But with age, such “exercises” become more and more difficult.
This type of wrinkles is usually formed in areas where our facial expressions “work” most actively – around the eyes, on the bridge of the nose, on the forehead. Therefore, they are called mimic wrinkles. In some literature they are also called Dynamic wrinkles. If you force the muscle to completely relax, then the wrinkle is magically smoothed out. The effect usually lasts for 3-4 months, after which the activity of the muscles is restored and the fold returns. Therefore, injections of Botox or Dysport need to be repeated from time to time. Sometimes, for reasons that are not completely clear, the effect of injections lasts no more than 6 weeks.
HOW BOTULINUM TOXIN WORKS
Botulinum toxin is a protein that can interfere with the transmission of impulses from the nerve to the muscle, thereby causing muscle paralysis. During normal impulse transmission, the neurotransmitter acetylcholine is released at the junction of the nerve end with the muscle (synapse), which causes muscle contraction. This is a rather complicated process. At first, vesicles containing acetylcholine approach the outer membrane of the nerve end. For acetylcholine to be released, the bubbles must merge with the membrane, which is impossible without a special “fusion complex” consisting of several proteins known as SNARE-complex. Botulinum toxin passes through the membrane of the nerve ending inward, and then “cuts off” certain proteins from the fusion complex. Each type of botulinum toxin has its favorite target. For example, botulinum toxin type A, which is what Botox is made from, attacks the SNAP-25 protein. Without a full-fledged SNARE, acetylcholine bubbles can no longer merge with the membrane and remain inside the nerve ending. As a result, even though the nerve fiber continues to send commands, muscle contraction no longer occurs.
AND YET IT IS POISON
The doses of botulinum toxin administered during cosmetic procedures are very small (several times less than those used in medicine and hundreds of times less than the lethal dose). This amount of toxin is enough only to relax the muscles lying near the injection site. And yet the mere fact that a deadly poison is injected into the skin cannot be ignored by many of us. What if the toxin somehow spreads further than it should? Can it cause any serious side effects?
According to the FDA, for the period from 1989 to 2003, botox injections resulted in the death of 28 patients. In 2008, the FDA issued a warning that the use of botox can cause respiratory failure and other serious health problems. To reassure all my dear customers, I would like to point out that in almost all these cases the described side effects happened with the medical use of botox, mainly in the treatment of spastic paralysis in children under 16 years of age. The FDA notes that in the US, the use of botox against children’s spastic paralysis is “off label”, which means that the doctor selects doses at his own risk and the doses are based on published data, doctor’s own experience and the experience of the colleagues. In contrast to cosmetic procedures, treating spastic paralysis requires significant doses, since it is necessary to eliminate the spasm in the large muscles.
Yet the risk of botulism, and even death caused by the cosmetic injection of botox is insignificant. However, botulinum toxin can indeed spread beyond the injection area and cause a series of issues. The thing is that the toxin is not programmed to fight wrinkles. It just blindly affects all the muscles that it is able to reach. If the poison spreads to the area where it was not planned to enter, the side effects can be serious. For example, after an injection made in the eyebrows, the poison can get into the muscles of the upper eyelid, which will remain half closed for the next 2-3 months. This will lead to dry eyes, tearing and general discomfort. Another complication is the drooping of the lips’ corners which leads to the effect of the “Greek tragic mask” and salivation. Asymmetry of the face is also possible due to uneven relaxation of the muscles on the right and left side, difficulty in swallowing and hoarseness of the voice which is caused by partial paralysis of the muscles of the larynx.
All these side effects are listed in the patient information leaflet which also provides recommendations for their prevention. In particular, botox is recommended to be administered gradually, in small doses, watching the reaction. The patient is advised not to massage the injection site as not to disperse the toxin through the surrounding tissues. However, sometimes there are unexpected side effects. For example, a small proportion of patients after botulinum toxin injections have severe migraine-like headaches. And sometimes it happens the other way around – headaches that have tormented a person for years after such injections suddenly miraculously disappear. One of the patients (the case is described in a medical journal) after the procedure with botox acquired a persistent metallic taste in the mouth. The mechanism of these side effects is not yet known, which means further research may surprise us.
Our desire to stay young and beautiful at all costs and our willingness to pay for this big money led to the fact that very risky methods are often used in modern cosmetology. It is well known that such procedures as liposuction (surgical removal of excess fat), phenol peels and mesotherapy can end badly, and in very rare cases even lead to death (sometimes during the liposuction a severe bleeding occurs; phenol has a toxic effect on the heart, and after mesotherapy treatment in rare cases, a difficult to treat body-eating infection of the connective tissues can easily develop).
Considering all the above, the use of deadly poison for smoothing wrinkles does not sound too bad. I, personally, believe that with the right choice of dose and administration method, as well as patient compliance with all the recommendations of a specialist, the risk of side effects is very small. And yet, the fact that botulinum toxin is a poison that easily penetrates the nerve’s tissue and selectively affects the molecular structures responsible for the transmission of nerve impulses, makes it necessary to treat this product with a great care.