Botulinum Toxin for Cosmetic Use


The History of Botulinum Toxin for Cosmetic Use

The FDA approved botulinum toxin for cosmetic uses in 2002. Contrary to popular belief, botulinum toxin has many uses that don’t involve treating wrinkles. Botulinum toxin (BT) was approved for cosmetic use after years of doctors noticing that patients treated with BT had improvement of the wrinkles between their eyebrows (aka the glabellar frown lines). BT was first used in humans in 1977, and it was approved for strabismus in 1979. Eventually, they extended the indications to include blepharospasm and hemifacial spasm. Finally, it was available to the rest of us in 2002 for the treatment of glabellar frown lines. BT injection is now the most common cosmetic procedure worldwide. That’s the short history of Botox. Most people use the word “Botox” for any brand of botulinum toxin, but as you’ll learn here all botulinum toxins are not the same. There are 3 brands: Botox, Dysport, and Xeomin.

How to Prepare for Botulinum Toxin Injections and What to Expect

Botulinum Toxin for Cosmetic Use

Where does Botulinum toxin come from?

Botulinum toxin is organic in the sense that it’s a protein made by a bacteria called Clostridium botulinum. The BT prepared for cosmetic use is Type A only. C. botulinum makes 8 serotypes of toxin, but only A is approved for cosmetic use.

The different brands of botulinum toxin differ slightly in how they make their product. Botox uses the Hall strain of C. botulinum to produce BT Type A and purifies it using acid precipitation. The end result is a mixture containing BT and the associated complexing proteins. Xeomin is made with an even more stringent process of purification. Xeomin has no associated complexing proteins. Dysport is purified using a column-based technique instead of acid precipitation.

How does botulinum toxin work to destroy wrinkles?

First, we have to start with a quick physiology lesson before we dive in. The reason your muscles are able to move is that your brain has neurons coming down to the muscles and telling them when to contract. The presynaptic motor neuron goes from the brain and ends at the neuromuscular junction. The neuromuscular junction is the space between the presynaptic motor neuron and the postsynaptic muscle fiber. The muscle fiber contracts when the presynaptic motor neuron tells it to.

neuromuscular junction botulinum toxin

The Neuromuscular Junction: Vesicles filled with acetylcholine leave the presynaptic neuron and bind receptors on the postsynaptic muscle fiber to initiate contraction.

BT works at the neuromuscular junction to block the release of acetylcholine from the presynaptic motor neuron.

Acetylcholine is the molecule that is normally released by the presynaptic motor neuron into the neuromuscular junction when it wants the muscle to contract. Muscle fibers that take in the acetylcholine will begin to contract.

BT gets into the presynaptic motor neuron by endocytosis. BT is made of a heavy and a light chain. The bond between the 2 chains is cleaved once inside the presynaptic motor neuron. The light chain interacts with the SNAP25 protein. SNAP25 protein function is to allow fusion of the acetylcholine filled vesicles in the cell’s cytoplasm with the cell membrane. Acetylcholine then goes outside the cell to act on the muscle fiber and cause it to contract. BT

SNAP25 protein’s function is to allow the acetylcholine filled vesicles in the presynaptic motor neuron to fuse with the cell membrane. Acetylcholine then goes outside the cell to act on the muscle fiber and cause it to contract. BT irreversibly blocks SNAP25 so acetylcholine never gets a chance to be released. If your muscles aren’t contracting, they’re not creating the wrinkles we see in the mirror.

Why isn’t botulinum toxin permanent?

Although BT’s effect are permanent on any one presynaptic motor neuron, the neurologic system is resilient. New nerve terminals will sprout in and around the blocked neurons in about 3-4 months.

What can botulinum toxin fix?

BT can only work to paralyze your muscles. It will reduce the looks of lines, but it won’t fill them in if they’re too deep. BT is indicated for glabellar frown lines (the serial 1s you see between your eyebrows), horizontal forehead lines, crow’s feet, and brow ptosis (when your eyebrows droop).

Serial ones glabellar frown lines

Glabellar Frown Lines

For the mid-face and nasolabial folds, doctors usually recommend fillers instead of BT.

Botulinum toxin is approved for several conditions by the FDA. This includes:

Glabellar frown lines

Axillary Hyperhidrosis

Strabismus

Blepharospasm

How often does botulinum toxin have to be redone? 

BT usually lasts between 3-4 months. Muscles slowly regain function as the lifespan of BT wears out. If you want to do BT long-term, you have to consider the risk of forming antibodies to the product. This means it would no longer give you the wrinkle-smoothing results you desire because your body is effectively neutralizing the BT before it can do its magic. In that case, you have to switch to a different BT formulation than the one you were using.

There is a very slim chance that your body may form antibodies to the botulinum toxin. This usually occurs to people receiving large amounts of botulinum toxins for other conditions. If you want to do BT long-term, you have to consider the risk of forming antibodies to the product. This means it would no longer give you the wrinkle-smoothing results. Antibodies to botulinum toxin neutralize the BT before it can work. One solution is switching to a different formulation of BT.

If you decide BT isn’t for you, then you never have to do it again. You can wait a few months for your facial muscles to regain their function again. If you realize that you either can’t afford or devote the time necessary to maintain BT upkeep every 3-4 months, you can inject less often.

How to Choose Between Botox, Dysport, and Xeomin

It’s easy to choose because the products are so similar. It all comes down to patient preference and price. Some patients started with Dysport and have found that they get the best results with Dysport. Botox doesn’t always work on everyone or forever with repeated use. Xeomin is the new kid on the block. Find out what your doctor prefers and what he or she has had the most success with. Just because your best friend raves about her results with Dysport, doesn’t mean Dysport is the best fit for you.

The difference between these 3 companies isn’t just the branding but the actual molecule you’re being injected with. Like I mentioned before, they are produced in slightly different ways. Another difference lies in the number of accessory proteins added to the BT. Botox is Onabotulinum toxin A. Dysport is Abobotulinum toxin A. Xeomin is Incobotulinum toxin A. (1) Botox is complexed with 750kilodaltons (kDA) of protein. Dysport is complexed with 250kDa of protein. and Xeomin has no complexing proteins. What does this mean for you? Ultimately, it doesn’t make much of a difference to the consumer.

The units between these companies are not interchangeable. 1 unit of Botox does not equal 1 unit of Dysport. It’s been found that 1 unit of Botox is equal to 2.5-3 units of Dysport. (3) Xeomin is equivalent to Botox in terms of units.

What is a unit of botulinum toxin?

1 unit of BT is equal to the median dose of BT required to kill a female Swiss-Webster mouse. (4) This random unit comes from the clinical trials done on BT. The measure of the unit is irrelevant to our discussion. It’s more important to know how many units you need for an area to be treated with BT.

How many units of botulinum toxin do you need?

This is entirely dependent on how wrinkly the areas to be injected are and how strong the muscles of the face are. If you are paying by treatment area, make sure you discuss their policy on fixing areas of undertreatment. You should be able to go back into their office and have them add more for free. If you are paying by the unit, make sure you are realistic on how much you will need based on your doctor’s recommendation.

If you want to know about averages, then you can expect about 25 units (for Botox) on your forehead and crow’s feet.

How many units am I really getting?

The bottle of botulinum toxin that your doctor buys comes as a powder that he or she has to mix with saline. This reconstitutes into the clear liquid you see being injected into your face.

The chart below compares the number of units, reconstitution volumes, and final concentrations of Botox, Dysport, and Xeomin.

Botox Dysport Xeomin
Units in 1 bottle 100 300 100
Recommended reconstitution volume 1-8mL 0.6-2.5mL 1-8mL
Actual reconstitution volumes 1-2.5mL 1.66-3.32mL 1-2mL
Final Concentration 12.5-100Units/mL 120-500U/mL 12.5-100Units/mL

Ask your doctor about his or her reconstitution method. If you’re paying by the unit, make sure you know how many units your treatment should take. If you’re paying by treatment area, find out how many units you got and figure out if you’re getting a good deal.

Does the method of reconstitution matter as long as I’m getting the same number of units?

According to some reports, yes. Some doctors believe that high dilution can lead to the diffusion of botulinum toxin to unwanted areas, and thus unsatisfactory cosmetic outcomes. (1) It’s also associated with a lower duration of results. Believe me, you want to get the most bang for your buck here.

How old is the botulinum toxin? When was it reconstituted?

Botulinum toxin doesn’t last forever on your face. Likewise, it doesn’t last forever in the bottle once it’s mixed with saline. Manufacturers recommend that the toxin is used within 4-24 hours after reconstitution and stored in the refrigerator. Most doctors find these recommendations to be too strict with negligible effects on patient results. If it’s been reconstituted within 2-3 weeks, you’re safe. Some doctors don’t see a lot of BT business and end up storing their product for more time than recommended. Make sure you’re going to a doctor who’s experienced and doing this procedure relatively often.

Botulinum Toxin Antibodies

When you use a lot of BT for a long time, there is a risk that your body will start developing neutralizing antibodies to the BT. The chance of this happening to you with normal cosmetic use is slim compared to those getting higher doses of BT for medical reasons. If you get BT for the first time and see no results, then you’re probably a primary non-responder. This is extremely rare. On the other hand, if you’ve been getting BT for years and your latest injections haven’t given you the results you’re used to or lasted less time, then you’re a secondary non-responder. Your doctor can check for the presence of antibodies with a blood test.

There are 2 types of antibodies that can be formed: neutralizing and non-neutralizing. Non-neutralizing antibodies are directed against the complexing proteins we talked about earlier. Neutralizing antibodies are directed at the BT toxin itself.

Neutralizing antibodies are the most clinically relevant because the complexing proteins aren’t involved in the mechanism of action. The development of neutralizing antibodies can be augmented by the complexing proteins inherent to your BT of choice. Alternatively, without complexing proteins present, this could be a natural response from your body to the BT. (2) The newest BT formulation, Xeomin, will likely have the lowest rates of antibody formation because it doesn’t have any complexing proteins.

What are the options when you develop antibodies to botulinum toxin?

The first step, assuming you want to continue BT treatment, is to switch to a different formulation. If you’ve always done Botox, try Xeomin. Alternatively, your doctor can try higher doses of BT. However, if you’re paying by the unit this may be prohibitive.

Contraindications to Botulinum Toxin

You should not receive BT if you’ve ever had an adverse reaction to BT in the past. You are at increased risk if you have a peripheral motor neuropathic disease, ALS, or a neuromuscular junction disorder (Myasthenia gravis or Lambert-Eaton syndrome) . This is why it’s important that your doctor obtains a full medical history beforehand. Be wary of a doctor that is just trying to inject as soon as you walk in the door.

Side Effects of Botulinum Toxin

Side effects are rare, and most people tolerate BT very well. Some of the more common reactions are injection pain, local swelling, redness, short lasting numbness, headache, and mild nausea. In 1-3% of cases, you can get temporary eyebrow droop. (4) This is due to migration of the BT from the site of injection to the levator palpebrae superioris muscle. You can decrease the chance of this happening by getting a good doctor who knows his facial anatomy, remaining upright for 3-4 hours after injection, not touching the area, and actively contracting the muscle treated to increase uptake of the toxin to that area while limiting diffusion.

How much should you pay for botulinum toxin?

Lastly, this is highly variable based on where you live and who’s injecting. A board certified dermatologist or plastic surgeon will always cost more than a nurse practitioner or other mid-level provider. Any doctor can inject BT, but not every doctor can do it well. I’ve seen prices around $10-15 per unit and treatment areas for $300-500. Most doctors will do discounts for loyal repeat patients. You just have to ask.

What else do you want to know about botulinum toxin for cosmetic use? Leave your comments below. 

References

  1. Trindade de almeida AR, Secco LC, Carruthers A. Handling botulinum toxins: an updated literature review. Dermatol Surg. 2011;37(11):1553-65.
  2. Benecke R. Clinical relevance of botulinum toxin immunogenicity. BioDrugs. 2012;26(2):e1-9.
  3. Ravenni R, De grandis D, Mazza A. Conversion ratio between Dysport and Botox in clinical practice: an overview of available evidence. Neurol Sci. 2013;34(7):1043-8.
  4. Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8-14.

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