Argireline: Botox in a bottle?

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I first encountered argireline touted as “Botox in a bottle”, probably in a fashion magazine or online blog. A quick google search told me that Deciem carried this specific ingredient as its own serum (hurrah!) under the The Ordinary line. Plonk it went into my online shopping basket, and soon arrived into my eager hands. I didn’t realise at the time, but I was already using this ingredient, as it is contained in The Ordinary Buffet serum. It was labelled under its INCI name, acetyl hexapeptide-8 (1). The other name for it is acetyl hexapeptide-3, as per the WHO Drug dictionary (1).

The Science of Argireline

Before I get into my personal experience with argireline, a little science. I’m not a cosmetic chemist, nor do I presume to be. And I also do not work in the cosmeceutical industry. If you follow me on Instagram, you’ll know that I recently reviewed The Ordinary Buffet serum, and tried to find some good quality evidence behind the cosmeceutical use of peptides. But I mainly found only in vitro studies (i.e. in a lab or petri dish), as opposed to in vivo studies (i.e. tested on humans). I suspect, but cannot be certain that a lot of these studies are industry funded, and as these molecules are proprietary, the studies may not be freely available in the public domain. But this is a guess. I suppose I could file a Freedom of Information request, but at the moment I don’t have any wish to.

Interestingly, information on argireline is more available. Argireline is a synthetic peptide that mimics the structure (i.e. the amino acid sequence) of the SNAP-25 protein (2). To understand what the SNAP-25 protein is, we need to back up a little. In extremely basic terms, one of the mechanisms that allows for muscle contraction is when specific naturally occuring molecules (neurotransmitters) are released at the neuromuscular junction (where the nerve ending meets the muscle). Neurotransmitters are usually packaged in little bags (vesicles), which need to fuse with their target tissue in order for the contents of the vesicles to be released.

Botox is the proprietary name for botulinum toxin (specifically botulinum toxin A) that is used in pharmaceutics or cosmeceutics. For the uninitiated, it is a neurotoxic protein released from the bacteria Clostridium botulinum, which inhibits the release of a neurotransmitter called acetylcholine at neuromuscular junctions, and therefore causes paralysis, which can cause death at toxic doses – a disease known as botulism. Now when the toxin is used for therapeutic purposes, the dose is carefully titrated to avoid toxicity.

This SNAP-25 protein is involved in this vesicular/target tissue fusion, and botulinium toxin inhibits this protein, among others, from working properly. Hence, when someone gets Botox for their wrinkles, they are literally inducing temporary muscle paralysis in order to relax wrinkles caused by the contraction of said muscles (i.e. relaxing dynamic wrinkles).

The Evidence for Argireline

When I searched Pubmed, there was one double-blinded randomised placebo-controlled study in 60 Chinese subjects, which showed that argireline was effective in reducing wrinkles compared to placebo (3). That’s a lot of jargon right there. Let’s break it down. Double-blinded means that both the participants and the researchers didn’t know who received argireline and who received placebo during the time of the study. The groups would only have been revealed after the experiment was complete. Placebo means that the subject was given something with no known therapeutic effect but with the intent of using that substance as therapy. So in this experiment, they either got the argireline serum (it was an oil in water emulsion) or just the oil in water emulsion without containing argireline. This is to control for the fact that with placebo alone, there can be up to 30% treatment effect (or something like it – this is from memory now!) – and this is for all placebos (pretty incredible the power of the mind). And randomised means patients were allocated to each group in a random fashion. So the design of the study, at least what you read on paper, is what you’d call “gold standard” in terms of evidence-based methodology.

What I can’t comment on is whether the outcome measures they used to determine wrinkle reduction were appropriate for what they were looking for, because I don’t work in this industry. What this means is that in order to find an effect of something, you have to use the appropriate measure for it. For example, if you wanted to determine how well a drug improved vision, but you defined improvement as anything better than 6/60 (this is the top/biggest letter of a vision chart), then almost everyone would “have an improvement” by this standard. Now imagine if you set the definition of improvement as anything better than 6/6 (this is your “20/20” vision). Far fewer people are going to hit that improvement level because the standard of what defines improved vision is far stricter.

For what it’s worth, what they reported was that those in the argireline group compared to the placebo group had a statistically significant improvement in the wrinkles (note improvement does not equal elimination!) (3).

Also, 60 patients is really not a huge number of patients, but it is I suppose an ok sized amount, because the only other in vivo study I could find was one in 10 patients (2). So perhaps it really is “Botox in a bottle”. However, it is telling that in a quick search, I could only find one in vivo study. (Bear in mind I didn’t do a systematic search, and this is no means a systematic review!)

What is interesting is that a pilot study found that argireline has some effect in treating blepharospasm (5). Blepharospasm describes a condition where involuntary contraction of the muscles closing the eyelids occur. One way of treating this is with botulinum toxin (or Botox) injections. A pilot study is a “tester” study – to see whether there are any legs in an experiment, and how to tweak it for a bigger study. This study was also was double blind, randomised and placebo controlled (5). In this study, the patients were already receiving treatment with Botox injections, but those who used topical argireline to the eyelids could go for longer in between their injections, which suggests that the argireline itself had some effect in prolonging the muscle paralysis (5).

A final “Science-y” note & how it ties to The Ordinary Argireline serum

The last thing to say about argireline is that in an in vitro study examining skin penetration (i.e. in a lab dish basically), the experimenters found that when a 10% oil in water emulsion of argireline was applied to the skin of hairless guinea pigs and human skin, only 0.01% (i.e. 100x less) was found absorbed to the epidermis of the skin. The epidermis is simply the top layer of skin. What this means is that very little is absorbed. But this is not necessarily a bad thing, because perhaps the molecule is toxic at greater doses. What is also interesting to note is that the serum from The Ordinary uses a purely water formulation, because they say that a “higher water content results in better utility” (4). I’m not sure what they mean by that exactly, as “utility” implies that something is useful. So is this because they find most people buying the product would not want to buy it if it contained oil? Or is it becasue the oil/water emulsion is extremely finicky to package and or dispense? Or is it because they have found that argireline is more effective in a purely water formulation? In any case, you cannot apply the study by Wang et al that I just quoted to The Ordinary Argirelene serum because the formulation is completely different.

My Experience

Really though, you want to know if I felt that argireline truly was Botox in a bottle.

I need to caveat my experience with the fact that I don’t have any deep wrinkles. I am blessed with good genetics on both sides of the family, where skin is concerned. Add in the fact I’ve been wearing sunscreen on my face religiously rain or shine since I was around 11, after an accident I had, and was advised by a plastic surgeon that this plus a hat for at least 6 months was required to prevent pigmentary scarring on my face.

So take from my experience what you will.

I have an extremely bad habit of furrowing my brow. When I’m upset, when I’m anxious, when I’m concentrating, or when I’m simply telling a story or empathising with someone else’s story! It did not help that I started doing a job where close work and attention to detail was required. Plus the added stress with this job. This just amplified how often I furrow my brow during the day. Growing up, my mum used to smooth it out and tell me to stop frowning, and it would to annoy me to no end, but she was really right. Who wants to have those angry 11’s?

Anyway. Just prior to the pandemic, I actually seriously looked into getting “baby Botox”. Not because of the wrinkle (it was still just one solitary fine line between my brows visible only to me), but because it seemed no matter how much I told myself not to frown, my two brows seemed permanently pushed against each other, and I could see the inner ends of my brows kind of “poking out” towards each other in a frowning expression.

In the end I decided not to get Botox. That’s a post for another day.

So with my first bottle of this serum from The Ordinary, my brows were not as contracted together as in 2019. I think the first time I used this was in 2015 or 2016. This is important to note because I hadn’t been long enough in this new job at this point. And with this first bottle, I did actually notice a very subtle improvement in my singular fine line between my brows.

So as a result, I think I carried on with it for another one or two bottles. But I didn’t notice any further improvement. Was this because of the serum itself? Or was this because of other reasons? Who knows. The point is, at most the effect of The Ordinary argireline serum on my very minimal dynamic wrinkle was very subtle anyway.

What’s better than Botox in a bottle

I discovered this by accident.

We come back to the pandemic. At that point in time, I was working really long hours with a long commute. Even without the commute, I’d found for some time that my job was just too much. I often said to my husband that ideally I wanted to work one day less a week, “just to take the pressure off”. But circumstances were such that I couldn’t. Then this pesky virus happened. And just like that, I wasn’t able to do my job in the same capacity. I was so burnt out at that point, I hadn’t realised how burnt out I was until after the fact. In the first few months following the first lockdown, I recovered. It took a few months, but one day I realised I was no longer insatiably tired, and the thought of work did not immediately fill me with dread.

I also noticed that my furrowed brow was gone. I still had that very fine line (the one that really only I could see), but the inner ends of my brows were no longer contracted together. And it was at that moment, I realised how much of an effect stress had on my facial expression, and secondarily on aging. This was the first time since around 2012 or 2013, I’d actually finally been able to truly rest, despite all the crazyness happening in the world around because of the pandemic. A lot of us have been reflecting on our lives during the pandemic, and realising that the rat race we were all consumed by prior to the pandemic had gotten a little bit crazy and a little bit out of control.

I wasn’t doing any more meditation than normal, though I was able to get back to a more regular exercise routine. So maybe the exercise had something to do with it, but I exercise fairly regularly anyway. The only changes were that I was able to sleep adequately for the first time in years; and most of the usual stressors with work were removed. We all know that chronic stress has implications for physical and mental health in the long run, in part because it predisposes the body to a chronic state of inflammation. And inflammation is a basic process involved in healing but also in disease. But this is beyond the scope of this post, which is already getting too long.

So, do not underestimate the power of stress in all aspects of your life – even in something as frivolous as wrinkles.

Hope you have a wonderful day. Until next time x

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References:

1. Kluczyk A, Ludwiczak J, Modzel M, Kuczer M, Cebrat M, Biernat M, Bąchor R. Argireline: Needle-Free Botox as Analytical Challenge. Chem Biodivers. 2021 Mar;18(3):e2000992. doi: 10.1002/cbdv.202000992. Epub 2021 Feb 8. PMID: 33482052
2. Blanes-Mira C, Clemente J, Jodas G, Gil A, Fernández-Ballester G, Ponsati B, Gutierrez L, Pérez-Payá E, Ferrer-Montiel A. A synthetic hexapeptide (Argireline) with antiwrinkle activity. Int J Cosmet Sci. 2002 Oct;24(5):303-10. doi: 10.1046/j.1467-2494.2002.00153.x. PMID: 18498523.
3. Wang Y, Wang M, Xiao S, Pan P, Li P, Huo J. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects: a randomized, placebo-controlled study. Am J Clin Dermatol. 2013 Apr;14(2):147-53. doi: 10.1007/s40257-013-0009-9. PMID: 23417317.
4. Kraeling ME, Zhou W, Wang P, Ogunsola OA. In vitro skin penetration of acetyl hexapeptide-8 from a cosmetic formulation. Cutan Ocul Toxicol. 2015 Mar;34(1):46-52. doi: 10.3109/15569527.2014.894521. Epub 2014 Apr 22. PMID: 24754410.
5. Lungu C, Considine E, Zahir S, Ponsati B, Arrastia S, Hallett M. Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. Eur J Neurol. 2013 Mar;20(3):515-8. doi: 10.1111/ene.12009. Epub 2012 Nov 12. PMID: 23146065; PMCID: PMC4747634.