Protease vs. PHAs: Which is Better for Sensitive Skin?
Both protease enzymes and polyhydroxy acids (PHAs) are widely known for their gentle exfoliating properties, making them excellent choices for individuals with sensitive skin who may not tolerate stronger exfoliants like AHAs and BHAs. While both options help remove dead skin cells without excessive irritation, they differ significantly in how they work, how frequently they can be used, and their overall impact on the skin barrier.
What is Protease?
Proteases, also known as proteolytic enzymes, are natural enzymes that our bodies continuously produce to facilitate various biochemical processes. Enzymes act as biological catalysts, meaning they speed up specific chemical reactions. Proteases, in particular, function by breaking peptide bonds between amino acids in proteins, playing a crucial role in digestion, wound healing, protein turnover, immune responses, and hormone regulation.
These enzymes are not only essential within the body but are also beneficial in skincare. When derived from plant-based sources like papaya, protease enzymes provide enzymatic exfoliation, helping the skin naturally shed dead cells in a non-abrasive and barrier-friendly way.
How Does Protease Work on the Skin?
Since protease enzymes naturally break down proteins, they can also target keratin, a structural protein that forms the outermost layer of the skin. This natural exfoliation process is known as desquamation, where the skin uses its own proteases to degrade the corneodesmosomes—the protein structures that hold dead keratinocytes together in the stratum corneum.
Desquamation is a slow, multi-step process that usually occurs over 28 days as the skin renews itself. However, various factors—such as aging and environmental stressors—can slow down this natural shedding process, leading to dullness, clogged pores, and rough texture. This is where protease-based exfoliants can help.
In skincare, protease enzymes mimic and enhance this natural desquamation process by gently breaking down corneodesmosomes – structures that bind skin cells -, allowing dead skin cells to detach and shed naturally. Unlike acids, which rely on low pH levels to weaken cell adhesion, protease exfoliants work without significantly altering the skin’s pH balance. Their mildly acidic pH (~4.5–5.5) closely matches the skin’s natural acidity, ensuring minimal barrier disruption. Additionally, proteases are hydrophilic, meaning they attract moisture, helping to keep the skin hydrated and smooth. Due to their surface-level action, protease enzymes can be used daily without the risk of over-exfoliation or excessive irritation.

How Do PHAs Work on the Skin?
PHAs (polyhydroxy acids) belong to the hydroxy acid family and are considered the gentlest type of chemical exfoliant. Compared to AHAs (glycolic, lactic acid) and BHAs (salicylic acid), PHAs have the largest molecular structure, which prevents deep penetration into the skin. Instead, they work at a minimal depth, making them less irritating than their smaller-molecule counterparts.
Unlike proteases, which exfoliate exclusively on the skin’s surface, PHAs function by weakening the corneodesmosome bonds that hold dead skin cells together. This process allows for gradual shedding while simultaneously providing hydration due to their humectant properties. PHAs are hydrophilic, meaning they attract water molecules, helping to reinforce the skin barrier and improve moisture retention.
For most circumstances, PHAs are best to be used 2-4 times per week. PHAs are very gentle in that they minimally penetrate the skin, although their low pH can likely disrupt the skin barrier if used too frequently. Proteases, on the other hand, can be used daily because of their surface-level exfoliation and seamless pH level.
Which One is Better for Sensitive Skin?
Both proteases and PHAs are excellent choices for sensitive skin, but understanding their key differences can help you determine which one is better suited to specific needs: Ultimately, if you have super sensitive skin and may find irritation from a PHA, protease enzymes will ensure no skin barrier disruption/irritation, whilst also drawing moisture to the skin. It’s important to consider that proteases provide surface-level exfoliation, whereas PHAs minimally penetrate the skin to weaken the corneodesmosome bonds holding dead skin cells together. For this reason, it will take longer to notice results from proteases, so PHAs would likely be the preferable option if your skin can handle it.
Bibliography
Trevisol, Thalles Canton, et al. “An Overview of the Use of Proteolytic Enzymes as Exfoliating Agents.” Journal of Cosmetic Dermatology, vol. 21, no. 8, Dec. 2021, pp. 3300–07. https://doi.org/10.1111/jocd.14673.
“Topical Skin Care and the Cosmetic Patient.” ScienceDirect, 2018, www.sciencedirect.com/topics/neuroscience/hydroxy-acids#:~:text=Hydroxy%20acids%2C%20also%20known%20as,%2C%20glycolic%20acid%2C%20oxalic%20acid. Accessed 4 Feb. 2025.
“Intramembrane Proteases.” ScienceDirect, www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/protease. Accessed 4 Feb. 2025.
Hoshikawa, Karina. “A Guide to Polyhydroxy Acids (PHA) in Skin Care.” Allure, 24 Jan. 2019, www.allure.com/story/what-are-phas-polyhydroxy-acids.
“Industrial Biotechnology and Commodity Products.” ScienceDirect, 2011, www.sciencedirect.com/topics/earth-and-planetary-sciences/protease#:~:text=The%20proteases%20with%20pH%20optima,from%20Bacillus%20and%20Streptomyces%20species. Accessed 4 Feb. 2025.“Implications of normal and disordered remodeling dynamics of corneodesmosomes in stratum corneum.” ScienceDIrect, www.sciencedirect.com/science/article/pii/S102781171500035X#:~:text=The%20principal%20functions%20of%20desmosomes,cells%2C%20i.e.%2C%20the%20epidermis. Accessed 4 Feb. 2025.