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Even though some skincare companies would like you to believe that neuropeptides work as if they're Botox® in a bottle, this is a wild exaggeration of their actual capabilities. Botox® is a neurotoxin, not a neuropeptide, and is derived from the Clostridium botulinum bacterium (specifically, it is known as botulinum or botulism toxin). It works only when injected into specific muscles of the face to paralyze them for a few months at a time. This is quite effective at relaxing expression lines but has the danger of leaving one expressionless as this neurotoxin truly does paralyze the surround tissues of the injection site(s). Because of the potential for unwanted side effects and lack of clear evidence showing the long-term safety of botulism toxin injections, we wouldn't recommend this kind of anti-wrinkle therapy or want to bottle its effects even if we could (it's simply too dangerous).


Neuropeptides, on the other hand, occupy a kind of gray area of skincare technology that is only beginning to emerge. Different companies use the term “neuropeptide” in different ways, but the most common and recognized use is in relation to the use of specific peptide proteins to relax contractions in key areas of the face that result in expression lines/creases. In this way it is easy to confuse them with having Botox-like effects (as many unscrupulous companies would lead you to believe in their product descriptions), but neuropeptides do not work in this dramatic fashion. Rather, neuropeptides focus on what is commonly called the relaxation of "micro-tension" in the skin (not the muscles under the skin) and are specifically designed protein peptides that act by reducing surface skin contractions to smooth fine lines and wrinkles.


Neuropeptide Mechanisms


For instance, some neuropeptides, like certain pentapeptides, work on expression lines via enkephalins in this skin. That is to say that they couple to the enkephalin receptor on the outside of the nerve cells, which initiates a cascade of reactions inside the neuron to decrease of its excitability. The cells contraction response is diminished and the release of acetylcholine is modulated, resulting in less tension in the skin.


In a similar manner there are specific dipeptides that are used in skincare formulations to reduce "micro-contractions" (i.e. smaller, more subtle actions in the skin that aren’t as dramatic as deeper facial muscle movements) by being antagonistic to the nicotinic acetylcholine membrane’s receptor (mnAChR). As the muscular nicotinic ACh receptors are blocked, the ion canal remains closed so that Na+ is not released and the muscles stay relaxed.


Some neuropeptides work by more complicated mechanisms. Acetyl hexapeptides and acetyl octapeptides, for instance, are intended to inhibit catecholamine release and the SNARE complex, which is a somewhat awkward acronym for "SNAP (Soluble NSF Attachment Protein) Receptor." More specifically, these peptides mimic the N-terminal end of the SNAP-25 and thus competes with SNAP-25 for a position in the SNARE complex, which results in a controlled destabilization so that it cannot release neurotransmitters as effectually. The final result of this process is that surface facial contractions are attenuated and thereby the accompanying expression lines are diminished.


Neuropeptides & Rapid Wrinkle Relaxing



Gamma Amino Butyric Acid, commonly written gamma-aminobutyric acid or simply abbreviated GABA, is a natural compound formed in the body by combining glucose with glutamine (an amino acid). Its specific role is as a neurotransmitter in the brain (and overall nervous system) that controls neuronal excitability, and in humans is responsible for the regulation of muscle tone. There are many supplements for sleep, anxiety, and relaxation that contain GABA as the active ingredient (from which there is a definitive calming affect when taken orally). In fact, there are many anti-anxiety and sleep medications designed around stimulating the release of GABA in the brain.


But does it have the same relaxing effect on wrinkles and skin tension when applied directly to the epidermis? Admittedly, the scientific literature on topically applied GABA is slim. Its safety profile is well established, but the evidence for its use in relaxing wrinkles specifically is more anecdotal than formal. But anecdotal evidence, while not a peer-reviewed study, is still a type of evidence, as even in our own internal tests with this compound there have been volunteers who have responded well to the application of formulas that contain GABA as the only active ingredient. It is important to note, though, that GABA itself is a large molecule, so it needs penetration enhancers formulated with it to be more effectively utilized in a topical product (the extract of the Gynostemma plant, sometimes called Jiaogulan, is often paired with GABA for this purpose, and for enhancing both circulation and antioxidant support in the skin).


So what can we conclude about GABA? That it would be great to see more peer-reviewed evidence supporting its use in topical formulas, but as it stands there is still promising unpublished testing that has been done with this ingredient that suggests it could have an ability to relax skin tension that results in fine lines. We feel that its use in a target-specific, topical formula is warranted if it is included as a compliment to other wrinkle-relaxing ingredients with more literature behind them.




Regardless of the method by which a specific neuropeptide acts, these actions are all somewhat temporary in that the relaxation only lasts a certain number of hours after product is applied. But they also can be thought of as somewhat cumulative in that studies have shown there are more dramatic anti-wrinkle effects when a product containing these neuropeptides is applied daily (i.e. after a few weeks expression lines, such as around the eyes or forehead, are diminished more by the application of the product than they were at the beginning of treatment weeks before).


It should be noted that peptides used in skincare are a numerous and varied bunch, so it is important that you read not only an individual product's ingredient list to discover the specific ones used, but that you also read the product's description because many peptides are similarly named yet impart vastly different results. Some pentapeptides, for instance, are used only for the stimulation of collagen synthesis in the skin, while others do not affect collagen but rather are intended for relaxing expression lines. In cases when you're not sure it's best to read the intended effects the product lists on its label to gain insight into the nature of the peptides used. In our products we do not use neuropeptides in products meant for application over the entire face, but rather feel they should be targeted in more area-specific formulas, such as those meant for the eyes and forehead.

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