Special Feature: Exploring the Evolution of Toxin

By Holly Carver / 02 Dec 2022

Three practitioners discuss how botulinum toxin and its uses have developed over the last 20 years, and provide considerations for the future

Botulinum toxin is the foundation of medical aesthetics, consistently proving to be the most popular treatment with an estimated three million procedures performed worldwide each year.1 For many years, there were only three products available in the UK market, until 2022 which saw the launch of three brand new toxins. As we head into 2023, we spoke to three aesthetic practitioners about what the future of toxin might hold, and what injectors should be considering when they look to use a new toxin. 

A brief history of toxin 

The first incident of the serious food-borne illness botulism was documented in the 18th century when the consumption of meat and blood sausages gave rise to many deaths throughout the kingdom of Württemberg in South Western Germany. The then-district medical officer Justinus Kerner published the first accurate and complete descriptions of the symptoms of food-borne botulism between 1817 and 1822, when he attributed the intoxication to a biological poison.2 Kerner also postulated that the toxin might be used for treatment purposes.

Modern botulinum toxin treatment in medicine was pioneered by scientists Alan Scott and Edward Schantz in the early 1970s, when the type-A serotype was used to correct strabismus. It was later propelled into the cosmetic sphere when Dr Jean and Alastair Carruthers discovered the use of botulinum toxin for wrinkles while treating patients for blepharospasms, observing that many of their patients were also getting an improvement in their lateral canthal lines. Their research on this was published in 1992.2,3 

Since then, botulinum toxin-A has developed in aesthetic medicine, with different formulations and uses of the product emerging. Botulinum toxin-B has been developed for use in muscle disorders in the US, but not yet for cosmetic use and isn’t approved in the UK. 


The first licensed toxin in the UK was Botox in 2001, initially indicated to treat hyperhidrosis. In 2002 it was further approved for the treatment of glabellar lines.4 Aesthetic practitioner Dr David Eccleston notes that the introduction of Botox into his treatment offering completely transformed his practice. “I was probably one of the first doctors in the UK to start using Botox. At that point, I was a GP with an interest in dermatology, and my dermatology patients were coming in asking about this new treatment they’d heard of that was sweeping the States. I treated one patient, who spoke to another patient, and within three months I had a regular flow of (mostly female) patients coming in to get their frown lines done – and I have to say, I was getting some very, very happy patients!” 

Over the next 10 years, two more toxins were released onto the market: Azzalure (known as Dysport in other markets) and Bocouture (Xeomin). “These were the holy trinity of toxin for a very long time,” Dr Eccleston comments. However, now the UK aesthetics specialty is seeing more new toxins emerge including Letybo, Nuceiva, and Alluzience – a ready-diluted toxin designed to make it easier for users. There are even more to come that are currently in their trial phase. 

Dental surgeon Dr Souphi Samizadeh notes that this evolution isn’t singular to the UK, with a range of products available from the East and West that practitioners and patients can choose from. She notes, “Type-A toxin preparations have been developed and manufactured in the UK, Germany and China, whereas a therapeutic type-B toxin was prepared in the US. I like to say that Botox is like the grandfather, and the rest are its siblings or children. To date, toxin has been used globally to treat a wide variety of conditions associated with muscular hyperactivity, glandular hypersecretions and pain, as well as in aesthetics.” 

Product selection 

Having had experience with all six available toxins on the market in the UK, Dr Eccleston recently added Nuceiva to his treatment portfolio, which was launched at CCR 2022. “I have found that this product does not move through the tissues as much as any of the other toxins I have tried, so I know if I put it somewhere it will stay there,” he says. “This enables me to have the utmost precision when injecting, knowing it won’t affect any undesired muscles.” However, he notes that this may make it a more difficult toxin for beginners. “If the product does not go directly into the muscle it will stay in an undesirable location, so if you are a relatively unskilled injector you will need to up your game – I would say this toxin favours highly-skilled artistic injectors,” he adds. 

Dr Eccleston states that although he is enjoying using Nuceiva, he still offers other toxins in his practice. This is because some of his long-standing patients who have been having Botox for years want to continue with something familiar that has consistently given them good results. “This shows that introducing a new toxin does not necessarily take business away from the other toxins in your clinic. However, what it does do is create a new cohort of patients, because some of the younger generations have heard about new toxins when researching aesthetic treatments and are coming in and asking for the latest product,” he says. “Personally, I like having a variety of different toxins to offer as it gives me choice depending on what the patient’s wants and needs are.” 

Similarly to Dr Eccleston, Dr Samizadeh likes to offer several brands of toxins in her practice. She explains, “I am happy using various brands and don’t necessarily have a preference, but what matters to me is that the ones I am investing in have a long safety and efficacy profile, as well as clinical studies to back this up. All toxins on the market differ through their manufacturing processes, formulations and assay methods-units of biological activity, so it’s important to remember they are not interchangeable.” As such, she notes that when choosing a brand, practitioners should get to know the individual product well, even if they have used another toxin before. “You should always research what the ingredients are, as well as how to correctly store and reconstitute the product. In addition, look at what the research says about volume, dosage, spread, migration and diffusion, what the onset of action and longevity is, as well as its potential interaction with other medication,” she says. 

Professor Syed Haq notes that he determines what toxins to use by observing what gives his patients the best and most natural results. He does so by looking at the principles of proven and evidence-based safety, longevity, consistency and speed of onset. “I have had experience with all of the major toxins on the market, but personally, I like using Letybo, Botox and Alluzience as they’ve given my patients the most satisfaction,” he notes. “Letybo is the only toxin that has been trialed on patients up to 75 years of age, as well as on a large cohort of male patients, so it’s imperative to have this clinical data behind it when understanding its use and in particular the patient group one is treating.” 

Toxin resistance 

A complication that is often discussed though not often seen, in relation to botulinum toxin treatments, is toxin resistance. This is extremely rare when noting the impact when considering the cosmetic use of the neurotoxin. Professor Haq explains, “Usually, when we hear about cases of toxin resistance, it is from people who have used a botulinum toxin for medical reasons, and have had the injections at higher doses, often frequently and from a younger age (under 18) over a prolonged period of time. The summation of doses and amount of toxin delivered therefore eventually leads to an increased risk of developing antibodies to the toxin, where their immune system starts is triggered to produce antibodies against the light chain of botulinum toxin. It should be noted that antibodies can be produced against other elements also (non-neurotoxin associated proteins and excipients).” He adds that the studies that

have been conducted to determine neutralising antibody production have often used the in vivo assessment based on antibody titres derived using an enzyme-linked immunosorbent assay kit. “This can often be somewhat inaccurate with high variability amongst suppliers,” he says, noting, “The temperature of the assay on the day, the standard curve, sample storage and ELSIA kit insensitivity can all have an impact. The use of plasmon surface resonance and looking at antibody protein interactions at the correct pH would be the gold standard method of determining the presence and later the level of neutralising antibodies in a given patient’s sera.” Botulinum toxin type-B can be used as an alternative for those who have seemingly developed resistance to all type-A botulinum toxin brands, however, these patients tend to develop resistance to type-B soon after for reasons that have not yet been fully identified.

Considerations for toxin in your business 

Professor Haq notes that after safety profile and efficacy, pricing is one of the main factors practitioners and clinics will need to consider in the next year or so, particularly as a result of the current economic crisis. He notes, “If newer toxins getting market authorisation do end up lasting for more than six months (which the ones currently being trialled are suggested to do), the practitioner is going to have to look at alternative ways to attract the patient to the clinic at the frequency which they are used to. Whereas before, they might have visited three or four times a year, it will become no more than two if wanting a neurotoxin aesthetic treatment. So, from a business perspective, you’re going to have to strategise and work out whether using this longer-lasting toxin might be worse for your business in the long run.” He notes that there may also be a dilemma as to whether treatment prices should be raised, and whether patients will be able to afford to come to clinic if this is the case. 

Professor Haq adds that the longer-lasting toxins may be a big draw for male patients and those who work out consistently, however, noting, “Stereotypically, men are a more active group, and their facial muscle bulk and intrinsic metabolic rate causes them to come and complain that the toxin treatment isn’t lasting long enough. In addition, male patients don’t tend to want to visit an aesthetic clinic as often as women do, so it may be more enticing that they only have to visit once or twice throughout the year.” Professor Haq notes that using longer acting toxins have many positive reasons to be adopted but practitioners should be cautious particularly when considering the dreaded treatment emergent adverse events; in particular lid or brow ptosis. If a toxin lasts much longer than those being currently used, then resolving complications would invariably take longer and that could be a significant problem in the future for the practice and the practitioner. 

In terms of readily diluted toxins, Dr Eccleston notes that although many find it to be easier and quicker, it means you are unable to tailor the dilution for the individual patient, so this is something you should weigh up before purchasing. He explains, “I will dilute my preferred toxin at a different dilution depending on the preferred result and the area of the face that I am treating, so a pre-diluted toxin wouldn’t work for me personally.” 

However, Professor Haq notes that it can be beneficial for many as it takes the guess work out of formulating the toxin and therefore may minimise practitioner error. He also advises that practitioners should choose their instrument carefully, noting that he personally prefers to use a 4mm 30-gauge needle. “This provides me with the consistency of depth, and it’s pretty painless. If you start to go for narrow gauge needles, you have to be very careful because the extrusion forces will change and that can lead to complications,” he notes. 

Dr Samizadeh notes that it is important for practitioners to be aware of some ethical considerations surrounding a product choice. She says, “For example, some products, including many skincare brands in the market, use animal testing and some botulinum toxin formulations include human serum albumin. For many patients, including vegans and those passionate about animal rights, this information would matter. Practitioners should put product ingredients on consent forms so that the patients can make an informed decision that would resonate with them, and the practitioner can offer an alternative.” 

The future of toxin 

Dr Samizadeh believes that, as with any aesthetic procedure, understanding your patient is crucial to conducting a successful treatment. “Their medical and cosmetic history are both important, as well as examining them both statically and dynamically. This way you can ensure you are tailoring your treatment specifically for them and getting the result they desire,” she says. 

Professor Haq agrees that one should assess the patient properly in a relaxed and fully animated state, taking pictures for medical records at each juncture. He says, “Following assessment, one can treat the patient in a patient-specific manner and not just using a standard injection pattern alone. Look, feel and identify the areas you’re going to inject. Also, ask the patient what their expectations are – what is it that they’re looking for and have they previously had any issues with toxin?” He recommends that if they are a new toxin user, you should review the patient within a number of weeks following treatment and check what their pattern of change was, so that in the future you can potentially manage the patient better. He continues, “You should do the same thing if you have a long-standing toxin user but decide to change the product you’re injecting to a different one on the market. Is it comparable to the results achieved before with a previously used toxin? If not, why might this be? Try and identify its pattern of action and more”. 

Dr Eccleston stresses the importance of going to training and continually updating your knowledge base and technique. He says, “I am still improving, even though I’ve been working with toxin for decades – my skill level now is more than it was a year ago and way more than it was five years ago. Do not go on a one-day course and think you are an expert. Getting good results requires experience and practice. I think everyone has been so obsessed with fillers for the last 10 years that the skillset when using fillers is far more advanced than it is with toxin, but this is changing now. There is definitely a lot more that is going to evolve regarding toxin in the next few years, and I can’t wait to be a part of it!” 

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