14 November 2008

Botulinum toxin in cosmetology — poison or medicine?

Candidate of Biological Sciences A. Margolina, "Science and Life" No. 9-2008

Botulinum toxin preparations (mainly botox) have gained popularity in recent years as a means for smoothing facial wrinkles, that is, wrinkles caused by excessive activity of subcutaneous muscles. For example, 11.5 million botox injection procedures were performed in the USA in 2006. Advertising claims that smoothing wrinkles with this poison is a fast, safe procedure with a low risk of side effects. Sometimes the authors of advertising articles go so far as to present Botox as a kind of non-toxic form of botulinum toxin that has nothing to do with a deadly poison. However, recently there have been reports of frequent cases of serious side effects and deaths associated with the use of this drug. So is Botox dangerous and what do we know about it at all?

Tamed Poison

In the 70s of the last century, American ophthalmologist Alan Scott began to test on his patients suffering from blepharospasm (involuntary closing of the eyes), an unusual medicine prepared on the basis of botulinum toxin, the most powerful natural poison that causes a deadly form of food poisoning — botulism.

The symptoms of botulism were first 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 arrest. Since in the past poisoning occurred more often when consuming sausages infected with the bacterium that produces this toxin, it was called botulinum toxin, that is, sausage poison (botulus means "sausage" in Latin), and the poisoning itself is botulism.

Although botulinum toxin is certainly dangerous, there was nothing unexpected in Scott's ideas, since back in the 1950s scientists established that purified and highly diluted toxin could, albeit with great caution, be used for medical purposes to relax muscle spasms. Soon, seeing a high percentage of cure, Scott's example was followed by other doctors, gradually expanding the scope of the toxin. In particular, botulinum toxin was used to treat strabismus and hemispasm (spasm of one half of the face). Even then, some doctors who treated patients with botulinum toxin noticed an interesting side effect. In the areas of injections on the face, there was a miraculous disappearance of wrinkles, for example, inter-brow folds on the forehead or folds in the corners of the mouth. Thus, the patient not only got rid of the annoying spasm, but also acquired a youthful, relaxed and friendly facial expression. Soon, a thin trickle of unusual patients - wealthy ladies over the age of 50, who were willing to risk everything in order to become younger at least for a while, reached the waiting rooms of neuropathologists.

There are several types of botulinum toxin, which differ in immunological and chemical properties. The first commercial drug containing botulinum toxin was botox. The manufacturers of the drug chose botulinum toxin type A (all types of toxin are denoted by Latin letters), which for a long time remained the only type of botulinum toxin used in medicine. Recently, drugs containing type B toxin have appeared. Other types of toxin are not used in medicine.

In 1989, the FDA (American Food and Drug Administration) officially approved the use of botox for the treatment of a number of diseases associated with involuntary muscle contractions. And although wrinkles were not yet listed in the list of indications for the use of this drug, more and more doctors began to use this medicine, as they say in America, "off label", that is, not for its intended purpose.

It was only in 2002 that the FDA finally approved the use of Botox (Botox Cosmetic) for cosmetic purposes - to eliminate facial wrinkles on the forehead and around the eyes. From that moment, Botox's triumphant ascent to the top of success began. It has come to the point that in the USA this procedure has become so popular that it is offered almost at every step — in beauty salons and even in sports clubs. In Europe and Russia, along with botox, the drug Dysport is used.

Such different wrinkles Let's talk now about where wrinkles come from and why they disappear after injections of botulism toxin.

Wrinkles, which upset women so much, not only look different, but have different causes. True age-related wrinkles occur due to changes occurring in the skin itself. Everything you have heard about the destruction of collagen and the accumulation of damage under the influence of UV radiation and other harmful factors refers to this type of wrinkles. But there are other wrinkles, which are just skin folds formed in place of the usual spasm of subcutaneous muscles. When the muscle contracts, it shortens and wrinkles the skin, and when it relaxes, it returns to its original position and "pulls" it back with it. Young women have elastic skin, it reacts quickly to such muscle movements and recovers, but with age, such exercises are already harder for her.

Such wrinkles are usually formed where our facial expressions "work" most actively — around the eyes, on the bridge of the nose, on the forehead. Therefore, they are called facial wrinkles. If you force the muscle to relax completely, then the wrinkle is magically smoothed out. The effect, as a rule, persists for 3-4 months, after which muscle activity is restored and the fold returns to its former place. Therefore, botox or dysport injections should be repeated from time to time. Sometimes, for reasons that are not entirely clear, the effect of injections lasts quite a bit — no more than 6 weeks.

How botulinum toxin works Botulinum toxin is a protein that can disrupt the transmission of an impulse from a nerve ending to a muscle, thereby causing muscle paralysis.

During normal transmission of an impulse, the neurotransmitter acetylcholine is released in the area of the connection of the nerve ending with the muscle (synapse), which causes muscle contraction. This is a rather complicated process. First, the bubbles containing acetylcholine approach the membrane (outer shell) of the nerve ending. In order for acetylcholine to be released, the bubbles must merge with the membrane, which is impossible without a special "fusion complex" consisting of several proteins (SNARE complex). Botulinum toxin passes through the membrane of the nerve ending inside, and then "cuts off" certain proteins from the fusion complex. Each type of botulism toxin has its own favorite target. For example, botulinum toxin type A, which is part of botox, attacks the SNAP-25 protein. Without a full-fledged SNARE, the acetylcholine bubbles can no longer merge with the membrane and remain inside the nerve ending. As a result, despite the fact that the nerve fiber continues to send commands, muscle contractions no longer occur.

And yet it's 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). All that this amount of toxin is enough for is to relax the muscles lying near the injection site. And yet the very fact that a deadly poison is injected into the skin cannot but worry. And if the toxin somehow spreads further than it should? Can it cause any serious side effects?

According to the FDA, between 1989 and 2003, botox injections led to the death of patients in 28 cases. In 2008, the FDA issued a warning that the use of botox can cause respiratory distress and other serious health problems. To calm the clients of beauty salons a little, we note that in almost all cases, the described side effects occurred during 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 United States, the use of botox against pediatric spastic paralysis is done "off label", that is, unofficially, which means that the doctor selects doses at his own risk, based on published data, his experience and the experience of colleagues. Unlike cosmetic procedures, the treatment of spastic paralysis requires significant doses, since it is necessary to eliminate spasm in large muscles. Nevertheless, due to the fact that we are still talking about deaths, the FDA has launched an investigation of all botulinum toxin drugs that are used in the United States.

And yet the risk of getting botulism, and even more so of dying after a cosmetic botox injection, is negligible. However, botulinum toxin can really spread beyond the injection and cause a number of troubles. The fact is that the toxin is not programmed to fight wrinkles, but simply blindly affects all the muscles that it can "reach". If the poison seeps into places where it was not planned to be injected, the effect may be tragicomic. For example, after an injection made in the eyebrow area, the poison can get into the muscles of the upper eyelid, which will remain half—closed for the next 2-3 months - the eye can neither be opened nor closed completely. This will lead to dry eyes, watery eyes and general discomfort. Another complication is the lowering of the corner of the lips, which leads to the effect of the "Greek tragic mask" and drooling. Facial asymmetry is also possible due to uneven muscle relaxation on the right and left sides (crooked smile), difficulty swallowing and hoarseness of the voice (partial paralysis of the laryngeal muscles).

All these side effects are listed in the annotation to the drug, which also provides recommendations for their prevention. In particular, the drug is recommended to be administered gradually, in small doses, observing the reaction. The patient is explained that the injection site should not be combed, so as not to disperse the toxin through the surrounding tissues. However, sometimes unexpected side effects occur. For example, a small proportion of patients have severe migraine-like headaches after botulinum toxin injections. And sometimes it happens the other way around — headaches that have tormented a person for years, after such injections suddenly miraculously pass. One of the patients (the case is described in a medical journal) after the botox procedure acquired a persistent metallic taste in her mouth, which "pleased" her just as much as the smoothed wrinkles. The mechanism of these side effects is still unknown, which means that further studies may still present surprises.


The desire of people to rejuvenate and become prettier at all costs and their willingness to pay a lot of money for it has led to the fact that very risky methods are often used in modern cosmetology. It is well known that procedures such as liposuction (surgical removal of excess fat), phenolic peeling and mesotherapy can end badly for the patient, and in very rare cases even lead to death (with liposuction, severe bleeding sometimes occurs, phenol has a toxic effect on the heart, and after injections of mesotherapy in isolated cases, it is difficult to develop curable "body-eating" connective tissue infection).

Against this background, the use of a deadly poison to smooth out wrinkles does not look out of the ordinary. Most specialists believe that with the right choice of dose and method of administration of the drug, as well as with the patient following all the recommendations of a specialist, the risk of side effects is low. And yet, the fact that botulinum toxin is a poison that easily penetrates into the nervous tissue and selectively affects the molecular structures responsible for the transmission of nerve impulses, makes it necessary to treat this drug with great caution. And it is worth considering whether it is reasonable to expose your nerves (and possibly brain cells) to the attack of sausage poison just in order to erase facial wrinkles from your face for 3-4 months — traces of thoughts and smiles?

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