Acetyl Hexapeptide 38: Cosmeceutical Use & Botulinum Toxin Alternative

Acetyl hexapeptide 38, which is also known as Argireline, is a peptide used in skincare products to reduce the appearance of wrinkles brought on by repeated facial expressions. When it comes to fine lines and wrinkles on the face, especially around the eyes and mouth; they usually form because of repeated facial expressions, such as smiling, frowning, or furrowing the brow in deep concentration or frustration. When people make these expressions, the face contorts based on the contraction of the muscles beneath the skin. Acetyl hexapeptide 38 is designed to temporarily reduce the appearance of wrinkles by intercepting messages from the brain, thereby preventing muscle contractions, similar to Botox. While this ingredient is considered to be safe there is the potential for it to travel through the bloodstream and generate muscle weakness. This is the case with any muscle relaxing peptide such as Syn-ake. If you experience a strong negative reaction to acetyl hexapeptide 8, then you should discontinue its use and consult your dermatologist or skin care expert.

Acetyl hexapeptide 38 in Cosmeceuticals

Skin aging is driven by both extrinsic factors (e.g., UV radiation exposure) and intrinsic factors (e.g., telomere shortening and the Hayflick limit), which occur simultaneously. Undeniably, aging affects the cells of the all layers of the skin. Histological changes related to this process are observable in the dermis, including collagen, elastin, and hyaluronic acid degradation; the increased production of matrix metalloproteinases (MMPs); and decreased fibroblast protein synthesis. The term “cosmeceutical”, while commonly used in scientific and marketing contexts, does not have a legally recognized status in the European Union. The term “cosmeceutical” is used in the functional sense to describe topical cosmetic products that contain active peptides like Acetyl hexapeptide 38 (AH-38) and demonstrate properties beyond basic skincare. Olsson et al. analyzed the public interest in the substance Acetyl hexapeptide 38. The study demonstrated an increasing interest in both the mentioned peptide and botulinum toxin. Acetyl hexapeptide 38 is gaining popularity as an alternative to botulinum neurotoxin, which may be attributed to its affordability, over-the-counter availability, and ease of application. The total peptide content in the receptor fluid amounted to a significant 30% of the amount applied to the membrane. This result indicates that Acetyl hexapeptide 38 has the ability to permeate through the stratum corneum.[1]

Due to the lipophilic properties of the stratum corneum, achieving therapeutic concentrations of hydrophilic active substances such as Acetyl hexapeptide 38, which poorly penetrate the skin, is challenging. The lipophilicity of the molecule that is to be applied to the skin plays a crucial role in penetration. Given the specific structure of the epidermis, not all molecules can pass through, but penetration can be facilitated by auxiliary substances and the chemical nature of the emulsion. The efficacy of emulsions containing Acetyl hexapeptide 38 has been studied by numerous research centers, but reports on penetration are limited, and even fewer have addressed the actual mechanism of action in the skin. Further research is needed to clarify the anti-wrinkle mechanism of Acetyl hexapeptide 38. There are still many unanswered questions that may lead researchers toward a better understanding of the action of botox-like peptides, ensuring they are both safe and effective. This review highlights the multifunctional properties of Acetyl hexapeptide 38, suggesting the potential to expand its indications for safe use, serving as an alternative to botulinum toxin.

Acetyl hexapeptide 38 as a Topical Alternative to Botulinum Toxin

Current data suggests that Acetyl hexapeptide 38 may improve wrinkle appearance, but the significance is unclear due to varying quantification methods. Utilization of it in a multi-ingredient topical shows more consistent and promising results, but formulations vary widely. Compared to botulinum toxin, Acetyl hexapeptide 38 has lower potency and toxicity with no serious adverse effects reported. Given the poor intrinsic cutaneous absorption of it, further investigation and development of vehicles of application for which are necessary. Larger studies with broader subject populations comparing the effects of Acetyl hexapeptide 38 with botulinum toxin using standardized methodology are also needed.

References

[1]Zdrada-Nowak J, Surgiel-Gemza A, Szatkowska M. Acetyl Hexapeptide-8 in Cosmeceuticals-A Review of Skin Permeability and Efficacy. Int J Mol Sci. 2025 Jun 14;26(12):5722. doi: 10.3390/ijms26125722. PMID: 40565185; PMCID: PMC12193160.

[2]Lum, Kalisa et al. “Acetyl Hexapeptide-8 as a Topical Alternative to Botulinum Toxin: A Review of the Literature.” Journal of drugs in dermatology : JDD vol. 24,4 (2025): e31-e32.

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