What a Toxin Scientist Taught Us About Botulinum Toxin
What Professor Andy Pickett, Toxin Scientist, Taught Us About Botulinum Toxin
For thirty years, one scientist has been doing something the aesthetic industry rarely welcomes: applying rigorous evidence to its most widely used treatment and challenging the myths that have accumulated around it.
This post is an extended version of our General Blog post on the subject.
A scientist in a clinician's world
Professor Andy Pickett occupies an unusual position in aesthetic medicine. He is not a clinician. He probably has never injected a patient. His background is pharmaceutical science, forty years working with biological products in the pharmaceutical industry, the last thirty of them focused almost exclusively on botulinum toxin.
He is Director and Founder of Toxin Science Limited in Wrexham, and Adjunct Professor at the Botulinum Research Center, Institute of Advanced Sciences, University of Massachusetts, and has delivered over 500 lectures on botulinum toxin and its uses to audiences worldwide.
What Dr Pickett brings to a field dominated by clinicians, industry representatives, and training organisations is something relatively rare: a deep understanding of what botulinum toxin actually is, how it actually behaves, and crucially, where the gap between the science and the received clinical wisdom is widest. That gap, it turns out, is considerable. And Pickett has spent much of his career pointing it out, sometimes to audiences who possibly would have preferred not to hear it.
The myths problem — a scientist's frustration
Pickett's most consistent and most publicly stated concern about botulinum toxin in aesthetic practice is the persistence of misconceptions that have no basis in the science. Over the years, certain misconceptions, errors, mistakes, and myths, notably about the different products used, have perpetuated. These have generally been linked to marketing efforts to differentiate one product from others.
The title of his 2019 paper in the Aesthetic Surgery Journal "Continuing Myths About Botulinum Toxin Use in Aesthetics Are Unhelpful and Unnecessary" is not a title chosen for diplomatic effect. It reflects the genuine frustration of a scientist who has watched marketing-driven claims repeated as clinical fact across training courses, conference presentations, and product literature for decades.
The brand equivalence argument
The most commercially sensitive of Pickett's positions, and the one most likely to generate resistance from industry, concerns the meaningful equivalence of the different licensed botulinum toxin products available for aesthetic use.
The marketed differences between products are considerable. Manufacturers have invested significantly in positioning their products as distinct from competitors, through claims about molecular size, diffusion characteristics, onset and duration profiles, and the presence or absence of complexing proteins. Pickett's analysis of the underlying science challenges most of these distinctions directly.
The existing evidence suggests that experienced users should achieve equivalent results regardless of BoNT-A formulation, but additional, well-designed, adequately powered, controlled randomised studies should be performed.
The complexing proteins argument, which holds that Botox and Dysport, which contain accessory proteins surrounding the toxin core, behave differently from Bocouture (Xeomin), which does not, is one Pickett has specifically examined. His position, supported by the available evidence, is that the complexing proteins dissociate from the neurotoxin before injection and play no meaningful role in clinical behaviour. The majority of differences between products seen clinically are, by far, due to simple dose differences used in studies, especially when two or more products are being compared.
The practical implication is significant. Practitioners who report meaningfully different clinical behaviour between brands, namely different onset, different spread, different duration are, in Pickett's view, primarily observing the consequences of different dosing conventions and different reconstitution practices rather than genuinely different biological activity from the same active molecule.
The products are not identical in formulation. In experienced hands, at appropriately calibrated doses, they are clinically equivalent.
It is worth acknowledging here, in the spirit of the evidence transparency we have written about elsewhere in this blog, that Pickett has held a senior scientific role at Galderma, the manufacturer of Dysport and Azzalure. A position that brand differences are largely marketing-driven is not without commercial convenience for a manufacturer whose products have sometimes been perceived as lower potency per unit than a competitor. His science is sound, but the context is worth noting.
The aftercare instruction question — where the science is most practically interesting
If Pickett's position on brand equivalence is the most commercially sensitive of his contributions, his analysis of post-treatment instructions is the most practically interesting for the clinical practitioner.
The standard aftercare instructions given to patients following botulinum toxin treatment e.g. do not lie down for four hours, do not exercise, do not massage the area, remain upright, avoid heat, are almost universally taught and almost universally given. They have the authority of established clinical practice behind them. What they do not have, according to Pickett's analysis, is meaningful scientific evidence.
The reason comes down to the biology of toxin binding. Most of the toxin is inside the neuromusclar synaptic vesicles within five to ten minutes after binding. Once the botulinum toxin molecule has bound to the presynaptic nerve terminal at the neuromuscular junction and been internalised into the synaptic vesicle, it is effectively committed. The subsequent steps, translocation of the light chain into the cytoplasm, cleavage of the SNARE protein, occur inside the cell and are not influenced by what happens at the skin surface or in the surrounding tissue. There have been no demonstrated alterations of effect from massaging or not massaging the areas injected post-treatment.
A large Italian retrospective study published in 2025, which cited Pickett's 2019 paper directly, provided clinical support for this position. A retrospective, multicentric study of 5,014 patients found that omitting extended post-injection instructions does not negatively impact patient satisfaction or complication rates. Given the toxin's rapid internalisation and localised effect, extended behavioural restrictions may be redundant.
There is no evidence that keeping the head elevated for six hours post-treatment reduces the chance of adverse events. The instruction persists not because the evidence supports it but because it has been taught, repeated, and institutionalised to the point where questioning it feels contrarian. This is precisely the kind of clinical myth that Pickett's 2019 paper title was aimed.
Dr Forrester heard a conference presentation on this topic by Dr Pickett, several years ago and abandoned almost all post-treatment advice at that point in time.
Given that one of the very few significant side-effects is upper lid ptosis, Dr Forrester has always believed that advising to keep the head elevated is completely counter-intuitive. This is because the eyelid elevator muscle (levator palpebrae superioris) lies immediately inferior to the lateral injection point of the corrugated muscle. So gravity would increase the likelihood of lid ptosis if the head were kept upright. If it weren’t for our knowledge of the rapid toxin binding, described above, we should be advising patients to avoid keeping their head up and lie flat after treatment!
The cooling question — a interesting finding
One of Pickett's less widely known but scientifically interesting positions concerns the use of ice or cooling before or after injection — a common practice for patient comfort and to reduce bruising. Cooling the treatment area might hinder BoNT-A translocation and should probably be abandoned.
The theoretical basis is sound, reducing tissue temperature slows metabolic processes including the internalisation of the toxin into the nerve terminal. If the toxin is bound at the surface of the presynaptic membrane but not yet internalised, cooling could theoretically slow or reduce the efficiency of that internalisation step. The clinical evidence for this effect is limited, but the mechanistic plausibility is real and it stands as an example of a routine clinical practice that has never been properly examined against the underlying science.
The bacteriostatic (preserved) normal saline finding — practically useful
On a more immediately practical note, Pickett and colleagues identified a finding that most practitioners will find directly useful. Manufacturer recommendations specify reconstitution of botulinum toxin products with sterile non-preserved saline. Compelling evidence suggests that reconstitution using preserved saline dramatically improves patient comfort without compromising efficacy.
The benzyl alcohol preservative in preserved saline appears to act as a local anaesthetic at the injection site, reducing the discomfort of injection significantly — with no evidence of any adverse effect on the toxin's activity or clinical outcome.
The one exception — masseteric treatment and post-injection muscle activity
The picture is not entirely one of abandoned instructions. Pickett acknowledges one area where post-injection behaviour does appear to influence outcome and the direction of the effect is the opposite of what conventional caution would suggest. The only study showing that post-treatment muscle activity by a patient can be beneficial demonstrated that masseteric muscle atrophy was significantly higher in patients who clenched their chewing muscles for two hours per day after treatment. Recommending chewing gum after masseter toxin would be sound clinical advice — although this evidence is very preliminary.
The mechanistic basis is plausible: active muscle contraction may enhance toxin uptake at the neuromuscular junction through increased recycling of synaptic vesicles. If confirmed in larger studies, it would represent a genuine evidence-based modification to post-injection practice — and a rather elegant inversion of the standard "rest the muscles" instruction.
What to make of Professor Pickett's contribution
Andy Pickett has done something that the aesthetic medicine field needs more of: applied the standards of pharmaceutical science to the claims, practices, and received wisdom of a rapidly growing clinical specialty.
He has challenged brand differentiation claims that are more marketing than science.
He has examined post-treatment instructions that are more convention than evidence.
He has identified practices i.e. cooling and certain aftercare restrictions that may be unnecessary or counterproductive.
And he has done so consistently, across hundreds of lectures and multiple peer-reviewed publications, with the rigour of a scientist rather than the authority of a clinician.
Not all of his positions are uncontested. The brand equivalence argument in particular continues to generate debate, and his industry affiliations are relevant context when evaluating his conclusions. But the core of what he has argued, that botulinum toxin practice in aesthetics carries more myth than most practitioners acknowledge, and that the science deserves more respect than the marketing it has accumulated is both well-evidenced and worth heeding.
For those of us who attended his lectures a decade ago and came away with the unsettled feeling that much of what we had been taught was more tradition than science, the published record confirms that the feeling was justified.
The views expressed in Clinical Perspectives are the Dr Forrester’s own and reflect his personal and professional experience of 15 years in aesthetic medicine.
References
Pickett A. Continuing Myths About Botulinum Toxin Use in Aesthetics Are Unhelpful and Unnecessary. Aesthetic Surgery Journal. 2019;39(5):NP150–NP151. https://doi.org/10.1093/asj/sjy300
Dover JS, Monheit G, Greener M, Pickett A. Botulinum Toxin in Aesthetic Medicine: Myths and Realities. Dermatologic Surgery. 2018;44(2):249–260. https://pmc.ncbi.nlm.nih.gov/articles/PMC5821482/
Nestor MS, Kleinfelder RE, Pickett A. The Use of Botulinum Neurotoxin Type A in Aesthetics: Key Clinical Postulates. Dermatologic Surgery. 2017;43 Suppl 3:S344–S362. https://pubmed.ncbi.nlm.nih.gov/33065958/
Pickett A. Dysport: pharmacological properties and factors that influence toxin action. Toxicon. 2009;54:683–9.
Talarico S et al. Are Post-Care Recommendations Following Upper-Face Botulinum Toxin Treatment Scientifically Necessary? A Retrospective Study Based on 5000 Patients. Toxins. 2025;17(8):372. https://pmc.ncbi.nlm.nih.gov/articles/PMC12390119/