BOTULINUM TOXIN

Botulinum toxin is an exotoxin produced by the anaerobic bacteria Clostridium botulinum. Structurally, this toxin is a polypeptide consisting of a heavy 100 kDa chain and a light 50 kDa chain connected by a zinc atom and a disulfide bond.

Botulinum toxin is a very potent poison that causes a specific form of food poisoning, which in most cases ends fatally due to progressive paralysis and respiratory arrest.

However, back in the 1950s, scientists discovered that highly diluted botulinum toxin could be used medically to relax muscle spasms. It began to be used to treat strabismus and hemifacial spasm (spasm of one side of the face), and as a side effect, a reduction in frown lines was observed.

In 1989, the FDA (U.S. Food and Drug Administration) officially approved the use of botulinum toxin in medicine, and in 2002, for aesthetic purposes as well.

There are 7 serotypes of botulinum toxin (A, B, C, D, E, F, G). Their mechanism of action involves preventing the release of acetylcholine at neuromuscular synapses. Serotype A is the most effective and currently the most widely used. It is the basis for the products Dysport (Ipsen, UK) and Botox (Allergan, USA), both officially registered in Estonia. Serotype B is also used — Neurobloc (Elan Pharmaceuticals), though it is not used in Estonia.

The dosage of these preparations is based on their biological activity and is expressed in units. The activity of the products differs significantly: 1 unit of Botox roughly corresponds to 2.5–3 units of Dysport, although this is only a very approximate conversion.

Brief description of the mechanism of action of botulinum toxin
Transmission of a nerve impulse from a nerve ending to a muscle fiber, causing muscle contraction, occurs at the neuromuscular synapse. This process works as follows: the synapse consists of the presynaptic membrane of the axon (the nerve ending itself) and the postsynaptic membrane of the muscle fiber. Between them is the synaptic cleft.
Inside the nerve fiber are numerous vesicles containing the neurotransmitter acetylcholine. These vesicles move to the presynaptic membrane, where they fuse with it and release acetylcholine into the synaptic cleft. There, acetylcholine binds to specific cholinergic receptors on the postsynaptic membrane. This generates an electrical potential, causing the muscle fiber to contract.
The transport of these vesicles depends on special protein complexes (SNAP-25, syntaxin, and synaptobrevin). These proteins are the target of botulinum toxin. By blocking them, the toxin blocks the synapse, preventing acetylcholine release. As a result of denervation, muscle weakness occurs, leading to the smoothing of facial expression wrinkles. Serotype A cleaves SNAP-25.

Pharmacokinetics

• Distribution of the toxin through the muscle and diffusion — 60 seconds to 3 minutes
• Binding to the receptor — 30 minutes
• Internalization of the toxin — 30–60 minutes
• Destruction of SNAP-25 — 4–6 hours
• After 24 hours, botulinum toxin is excreted through the kidneys
• The effect of the drug begins on days 2–4, reaching its maximum 2 weeks after the procedure

The destruction of SNAP-25 is irreversible. Recovery of muscle activity occurs because the damaged axon begins to form new terminal branches, known as “sprouting,” which lasts about 3–4 months. Therefore, there is no single answer to the question, “How long does botulinum toxin last?” Everything depends on the individual ability of the body to restore nerve endings. The normal duration is considered to be 2–10 months. From personal experience, the effect most often lasts 4–6 months, after which the procedure must be repeated. However, while the botulinum toxin is active, facial expressions also change: muscle spasticity decreases, the muscle becomes weaker and less active. Therefore, some patients do not feel the need to repeat injections immediately after the effect wears off and only undergo the procedure once a year.

Another remarkable effect of botulinum toxin should also be mentioned: after injections, many patients notice that headaches caused by muscle tension disappear.

Botulinum therapy is also successfully used to treat hyperhidrosis (excessive sweating) of the underarms. In this area, the effect lasts from 6 to 10 months.

What can influence the effect of botulinum toxin?

• Since botulinum toxin protein is zinc-dependent, a zinc-rich diet may positively affect the duration of the effect. A specially developed supplement for this purpose is Zytaze.
• Alcohol, vitamin A, and calcium supplements reduce zinc absorption.
• After the procedure, patients should actively make facial expressions for 30 minutes — this prolongs the effect.
• Plasma lifting procedures should not be performed for 2 weeks before botulinum toxin injections.
• Echinacea promotes faster recovery of nerve endings, meaning the effect of botulinum toxin may wear off sooner.
• The effect of Botox may also diminish with increased blood circulation: frequent sauna visits, intense sports, physical exertion, alcohol consumption, and certain cosmetic procedures (massage, ultrasound, microcurrents).

Indications in cosmetology
It should be remembered that botulinum toxin neutralizes muscle movement and is not a wrinkle filler. Therefore, its indications are limited to the correction of dynamic facial wrinkles, most of which are located in the upper third of the face:

• Horizontal forehead wrinkles
• Vertical frown lines between the eyebrows
• Wrinkles on the bridge and sides of the nose
• Crow’s feet around the eyes

In the lower third of the face, the following can be corrected:

• Perioral “smoker’s” lines around the lips
• Drooping corners of the mouth
• Chin wrinkles
• Neck wrinkles

Contraindications, there are relatively few:

• Age under 18
• Any disease involving impaired cholinergic transmission
• Botulinum toxin should not be used simultaneously with aminoglycosides or muscle relaxants. Pregnancy and breastfeeding are also considered contraindications due to the lack of clinical studies
• Throughout the use of botulinum toxin products, no cases of allergy to the toxin itself have been described, though reactions to auxiliary components are possible

What age is most suitable for botulinum toxin injections?
Each person is very individual, so there is no universal answer. I would say it is easier to prevent than to treat.

• Under 25 — the skin’s ability to recover independently is very high, so there is usually no need for the procedure
• 30–40 years — the effect is most noticeable because, once the cause of wrinkle formation is removed (muscle immobilization), the skin still has strong regenerative potential
• 50–60 years — the effect is still pronounced, but a combined approach with other treatments, such as hyaluronic acid preparations, is usually needed
• Over 65 years — the effect exists but is minimal; more radical methods are generally required