“My botulinum toxin didn’t last!” What impacts neurotoxin longevity?
The longevity of botulinum toxin injections causes much debate, with various anecdotal experiences from different patients and practitioners, particularly following the recent COVID-19 pandemic where some patients were reporting to their aesthetic clinicians that their results did not seem to be as long-lasting as usual.
In this blog, Dr Tim Pearce will look at what is going on, what can impact on the longevity of botulinum toxin injections, and what clinicians can do to try to increase this for patients to get the best from treatment.
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Manufacturing factors that may affect botulinum toxin longevity
Botulinum toxin type A is a complex, three-dimensional protein made up of a heavy and light chain. Anything that disrupts that shape – temperature, pH, time etc. – could stop it from working.
There are various brands of botulinum toxin that are licensed for cosmetic use in the UK including Botox®, Azzalure™ (Dysport®), and Bocouture™ (Xeomin®), with more becoming available as we speak. Most of these botulinum toxin type A products are similar in nature, but there are some key differences which may make them more vulnerable to damage, and impact on our ability to predict results.
For example, how the product is stored – which should be in accordance with approved and validated manufacturer guidelines – and the difficulties that may present to you, as the practitioner if you must regularly check refrigerators, for example. Unlike other brands, Bocouture does not require refrigeration and can be stored at room temperature. This may provide a more predictable outcome as it removes the risk of not maintaining the constant cold temperature required by others. In theory, those products requiring cold storage could be less resilient to being left out of the fridge for several hours or held up in the supply chain, although data is lacking to verify this, and much anecdotal evidence exists to the contrary.
All botulinum toxin brands note that once the freeze-dried product is diluted with saline, the vial should be stored in the refrigerator and used within 24 hours. Although, arguably, if you have a sterile vial (diluted with bacteriostatic saline) that is left out of the refrigerator for 24 hours, Dr Tim does not believe there is much chance of infection, the only risk would be that the botulinum toxin may not be as effective. Similarly, studies have shown that diluted botulinum toxin, used after four weeks behaves no differently, so is storage time really a factor affecting longevity?
Another theoretical factor related to manufacture which may affect longevity is the stabilising proteins within each brand, or lack thereof; Bocouture has fewer stabilising proteins than Azzalure and Botox. How these differences directly impact each product is likely to be a heavily guarded commercial secret.
Could the efficacy of the vial vary or taper off as it gets closer to its use-by date? This is simply a theoretical question, and Dr Tim suspects that if a product is in date and has been stored correctly then it is very unlikely that a significant difference would be so apparent.
Patient factors that may affect botulinum toxin longevity
If we assume that our botulinum toxin product of choice has been manufactured appropriately, is within date, and has been stored correctly, then another factor which may affect the longevity of treatment results is the individual patient.
Consider making a note when patients complain about longevity issues and if the weather – such as the recent heat waves we keep experiencing in the summertime – could be having an impact. Dr Tim believes that a ‘hot’ patient may experience less effect from botulinum toxin, and there is a reason for this. Upon injection the diluted botulinum toxin will spread around the interstitial space and settle as it gets to work. New blood will be being pumped into the interstitial space all the time and drained through the lymphatics; this is a constant process within the tissue, exactly where we are injecting the botulinum toxin. Thus, you have a limited period after injection for the botulinum toxin to get into the right place, otherwise, it will be washed into the systemic circulation. Therefore, anything that increases the flow of interstitial fluid is going to change the efficacy of the botulinum toxin; if your patient is hot, there is more blood in their skin, and you may lose some of the dose delivered before it can denervate. It takes approximately twenty minutes for botulinum toxin to settle on the nerve and achieve its goal. As always, we do not have adequate data to validate this hypothesis.
Another factor which may affect longevity is the time between treatments. Many patients have regular appointments – every three to four months as movement starts to return – to maintain the efficacy of their results. However, if this is interrupted, as happened with the closure of many clinics during the government designated coronavirus lockdowns in 2020 and 2021, their muscles start to move once more, get exercised, hypertrophy, and strengthen. This directly affects the efficacy of long-standing dosing patterns for a given patient, who may now complain of reduced benefit. They will require a higher dose to achieve the expected longevity experienced with former treatments.
Genetics can also impact on the longevity of botulinum toxin results for wrinkle relaxation. Some patients will respond differently due to differences in their receptors, their anatomy which can affect muscle size, shape, and strength, or rarely an immune difference which causes toxin resistance – an existing antibody or development of an antibody from previous exposure to all or some brands of botulinum toxin.
Clinician factors that may affect botulinum toxin longevity
Good injection technique is vital, and in this case, we are less focused on injection safety with botulinum toxin (compared to when we discuss dermal fillers and the risk of vascular occlusion), but more on avoiding the loss of product which can reduce the dose being delivered.
Dr Tim highlights how to avoid wasting valuable neurotoxin. For example, if you leave a tiny bubble in the syringe, then as you pull out, that bubble, which is initially compressed sometimes decompresses and squirts product on the surface of the skin, wasting a tiny amount. Find more top tips by reading 7 things you can do to stop wasting Botox.
Similarly, if you inject intravascularly, it will not beharmful, but you will lose that quantity of product as it flushes through the system without affecting the muscle. This is more likely if blood vessels are dilated in hot weather.
Aftercare factors that may affect botulinum toxin longevity
It is important that patients understand and follow the aftercare guidance provided, as this may also affect both the initial result and the longevity. For example, if a patient does something that exerts them, like exercising straight after their appointment, or makes their skin hot by visiting the sauna or spa, then in theory this is a very vulnerable time for the efficacy of the botulinum toxin. As previously mentioned, the first 20 to 30 minutes after the procedure are when the neurotoxin is engaging with the nerve, being hot may negatively impact this process.
Dr Tim’s take-home message is that it is very difficult to pinpoint exactly what may or may not be affecting the longevity of botulinum toxin treatments and contributing to perceived increases in patient complaints; aesthetic clinicians should diligently control the things they can control, observe their patients and learn from them, and report any unusual findings to manufacturers and pharmacies (with batch numbers) if they suspect any erroneous happening.
If you have any questions or comments about the longevity of botulinum toxins, you can find Dr Tim Pearce on Instagram.
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Botox® is a registered trademark of Allergan Aesthetics plc.
Azzalure™/Dysport® are registered trademarks of Galderma SA and Ipsen Biopharm Ltd.
Bocouture™/Xeomin® are registered trademarks of Merz Pharma Group.
Aesthetics Mastery Show
What REALLY impacts toxin longevity?
In our survey, 73% of clinicians had seen a rise in the number of patients complaining that their toxin has not lasted well. In this Aesthetics Mastery Show, we explore what factors really impact toxin longevity and what clinicians can do to improve the variables they have control over. Watch the full Aesthetics Mastery Show here.
The show has been watched over 17k times and has generated comments and debate from both practitioners and clients, including:
Gordon Boyle said:
“Great video guys! As a novice injector I note your comment about losing product on the surface of the skin! I’ve noticed the hub of my needle slipping from the syringe when exerting pressure on injection and thus product leakage and loss – any preventative advice for this ? Luer Lock syringe / depth of injection?”
Viewer Jae replied:
“I’ve noticed if there is a bit of resistance i.e pt is tense it increases pressure and can cause the needle to slip off the snug fit syringe to advance the a bit more, that usually does the trick”
In a separate discussion, Dandeli0n asked:
“How can a muscle that has been using Botox get even bigger than before when it has been relaxed for so so long? I don’t understand that.”
“It’s the gap between treatments that allows muscles to grow.”
Dandeli0n also asked:
“Can injectors cheat with dilution of botulinum toxin at all?”
To which Tim responded:
“yes- but there’s no point in the long term because you lose your patients. Happens when people first start out, and usually because they try and be cheap or they are scared of side effects.”
Read more questions and answers or join in the debate on our YouTube channel.
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