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.

On social media, you may have heard influencers promote the idea that having a healthy gut is the most crucial factor for healthy skin, more so than a skincare routine. I decided to investigate the gut microbiome’s correlation with the skin, measure the impact of the microbiota on skin conditions, and how to improve your gut health.

What is the gut microbiota?

The gut microbiota is the collection of microorganisms – bacteria, viruses, fungi – located in the gastrointestinal tract. This means that the intestines are strongly connected with the health of the gut microbiome. The gut microbiota facilitates several of the body’s functions, including protection against pathogens – disease-inducing agents -,  strengthening the immune system, metabolism, the health of the gut barrier, etc.

How does the gut microbiota relate to the skin?

The skin’s health is largely determined by the immune system, as it provides the skin protection from the external environment. The skin contains various immune cells that are populated with microorganisms. The community of these microorganisms inhabiting the skin’s cells is referred to as the skin microbiome, which is interconnected with the gut microbiome. These immune cells rely on the gut microbiome for regulation, enabling them to protect the skin from pathogens and inflammation. An unhealthy gut microbiome – otherwise referred to as dysbiosis – can lead to various skin conditions including eczema, psoriasis, acne, rosacea, skin cancer, etc.. The relationship between the gut and the skin is often called the gut-skin axis. 

How does dysbiosis cause skin conditions?

As the gut microbiome is strongly correlated with the skin, dysbiosis can lead to various conditions. Inflammation from dysbiosis can trigger the body to excessively release cytokines – proteins that regulate inflammation. When cytokines are excessively released into the bloodstream, they start to irritate the skin, causing skin conditions like rosacea. Atopic dermatitis – or eczema – can be caused by dysbiosis as well, as an imbalance in the gut is linked with a weakened immune system, thus making the skin more sensitive to environmental factors. When the skin is more vulnerable and sensitive, it’s more susceptible to developing inflamed, itchy rashes – a common symptom of eczema. In general, an imbalanced gut microbiome is detrimental to the proper physiological functioning of the body, ultimately leading to skin conditions.

Improving gut health with diet

Several dietary modifications are linked with improved gut health, including probiotics, lemon, ginger, and an increased intake of dietary fiber. These modifications all are linked with the production of butyrate – a short-chain fatty acid produced in the gut. Butyrate serves a valuable role in the gut microbiome, an essential component for a healthy gut.  supporting its function and regulation, providing energy for gut cells, and reducing inflammation. The large intestine relies on butyrate as an energy source for its colonocytes – cells that support the large intestine’s function – and thus, a healthy gut. In general, it’s best to avoid excessively processed foods and refined sugars, as these foods can inflame the gut microbiota.

In brief, the gut microbiome is strongly correlated with skin health. An imbalance in the gut microbiome – dysbiosis – hinders the proper functioning of the body, particularly the immune system. When the body fails to function and support the skin barrier properly, the skin barrier deteriorates. For this reason, following a healthy diet is essential to a healthy gut and ultimately, healthy skin.

Works Cited

“Gut–Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions.” National Library of Medicine, pmc.ncbi.nlm.nih.gov/articles/PMC7916842/#:~:text=The%20microbiome%20plays%20an%20important,by%20an%20altered%20gut%20microbiome. Accessed 13 Dec. 2024.

“Introduction to the human gut microbiota.” National Library of Medicine, 16 May 2017, pmc.ncbi.nlm.nih.gov/articles/PMC5433529/. Accessed 4 Dec. 2024.

“Signs of an Unhealthy Gut and What to Do About It.” Healthline, www.healthline.com/health/gut-health. Accessed 13 Dec. 2024.

Keratin is a crucial protein that your body constantly produces; keratin is essential for the function and maintenance of the skin, hair, and nails. Neglecting keratin can lead to several skin/hair issues, so it’s important to properly understand the role of keratin and how you can manage it.

What is keratin?

Keratin is a protein, meaning that it’s composed of a chain of amino acids. Keratin can be categorized as either hard or soft keratin. There are over 50 types of keratin, hard keratin and soft keratin are just to name a few. Hard keratin tends to be sturdier and less elastic, which can be found on the hair and nails. Soft keratin is more elastic, which is found on the skin, preventing the skin from sagging (the skin loses elasticity with age). Keratin is an essential protein in the structure of the skin, hair, and nails, but how exactly does it support them?

Keratin in the skin

The skin consists of three layers: hypodermis, dermis, and epidermis. The epidermis is the top layer of the skin, responsible for forming a protective barrier, protecting the skin from pollutants and irritants. The function of the epidermis is accredited to soft keratin, which is created by keratinocytes in the stratum basale – the deepest layer of the epidermis.

Keratin in the hair

Similarly to the skin, the scalp has a dermis and epidermis, with the dermis containing hair follicles. Hair follicles store keratinocytes, which distribute hard keratin from the hair follicle to the hair shaft – the hair that extends beyond the scalp. The hair shaft is almost entirely composed of keratin, which provides the hair with protection, strength, elasticity, etc.

Keratin hair treatments

Although keratin is constantly produced by hair follicles, keratin production decreases with age. Not only do keratinocytes experience lowered cell turnover, but keratin on the surface of the hair starts to break down in response to UV rays from the sun. For this reason, keratin treatments are offered by hair stylists, which is a process that takes a couple of hours. Keratin treatments are enriched with artificial keratin protein to straighten hair and reduce frizz. 

Keratin in nails

Similarly to the hair, nails are primarily composed of hard keratin. Keratin is being constantly produced by the matrix of the nail, which gets pushed out to grow the nail and provide its protective surface.

(https://my.clevelandclinic.org/health/body/24734-nail-matrix)

As we’ve established, keratin is an essential protein in the structure of the skin, hair, and nails, providing protection and strength. Unfortunately, as we age, keratinocytes produce less keratin, and keratin breaks down/gets damaged. However, you can combat this with a proper diet and lifestyle habits.

Boosting keratin production with diet:

In order for a nutrient to boost keratin production, it has to be associated with protein synthesis. Biotin is a B vitamin that has been shown to boost the metabolism of amino acids, and thus keratin synthesis. Protein and vitamin A have also been shown to stimulate protein synthesis. Incorporating foods rich in nutrients like biotin, protein, and vitamin A can boost keratin production in the body.

As we’ve learned, keratin serves the common purpose of protection and elasticity in the skin, hair, and nails. Although keratin is naturally produced by the body, keratin levels decline over time. For this reason, you can modify your diet to boost keratin synthesis in the body, or maybe consider a keratin treatment to replenish keratin in the hair.

Bibliography

https://www.cancer.gov/publications/dictionaries/cancer-terms/def/keratin

https://health.clevelandclinic.org/keratin-treatments

https://www.ncbi.nlm.nih.gov/books/NBK513133/#:~:text=The%20part%20that%20we%20call,the%20nail%20bed%20beneath%20it.

https://www.healthline.com/nutrition/keratin-rich-foods#:~:text=Keratin%20is%20a%20type%20of%20protein%20that%20boosts%20the%20health,keratin%20production%20in%20your%20body.

https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/keratin#:~:text=Keratin%20can%20be%20divided%20into,and%20contains%20approximately%2014%25%20cystine.

You may have heard that you should wash your face with warm water to open up your pores – allowing the cleanser to penetrate deeper- and finish off with a cold rinse to close your pores. This theory comes from the idea that heat increases the kinetic energy of atoms, thus making the pore expand; vice versa for cold water.

To determine whether or not this theory is true, it’s important to first understand the biology of the skin.

Anatomy of the skin

The skin comprises three layers: hypodermis, dermis, and epidermis.

The hypodermis (subcutaneous layer) is the deepest layer in the skin that is responsible for simply storing connective tissue; consisting of collagen and elastin, these tissues work to repair wounds, store fat, and insulate. This layer isn’t technically considered part of the skin, as it primarily serves to connect and protect the body.

Above the hypodermis lies the dermis, which is responsible for fostering hair follicles, blood vessels, sebaceous glands, and sweat glands. The blood vessels support the function of the epidermis. The sebaceous and sweat glands lubricate the hair follicle, which then travels to and moisturizes the skin.

The outermost layer lies the epidermis, which is composed of cells that get gradually and naturally exfoliated by newer skin cells. This layer contains the stratum corneum, which is a layer that acts as a barrier for the skin, protecting it from outside irritants. Sweat glands, sebaceous glands, and hair follicles bleed into the epidermis to form openings on the surface of the skin. These openings are known as pores, which allow these glands to escape. The body has over 5 million hair follicles/pores!

Can pores open and close?
As pores are simply openings to hair follicles and glands on the epidermis rather than cells, the water temperature cannot expand nor contract pores. Pores do not have kinetic energy that responds to a change in temperature. 

Luke-warm water is the best option
Given that the water’s temperature doesn’t directly open/close pores, it’s still beneficial to use warm water on your skin. Hot water damages cells called keratin on the epidermis, which can weaken and dry out the skin barrier. The high kinetic energy of the hot water will irritate/weaken the stratum corneum, ultimately drying it out and hampering its protection from irritants. Cold water, on the other hand, doesn’t damage the skin barrier; however, it still isn’t optimal when cleansing the face because it doesn’t dissolve the cleanser as well. Although cold water can reduce inflammation and increase blood circulation, by using lukewarm water, you’re receiving the benefit of faster-moving and more soluble water, while not damaging the epidermis. Warm water will optimize your cleanser’s ability to dissolve excess oil on your face.

As we’ve proved, the biology of the skin shows that pores can’t open/close in response to water temperature, since they are openings to the epidermis rather than cells. The appearance of congested pores is often confused with “open pores.” If you wish to target large, clogged pores, I recommend incorporating an exfoliating acid into your routine.

Bibliography

“Anatomy, Skin (Integument).” National Library of Medicine, 17 Oct. 2022, www.ncbi.nlm.nih.gov/books/NBK441980/#:~:text=The%20skin%20is%20primarily%20made,functions%20of%20the%20skin%20include. Accessed 18 Oct. 2024.

Hasudungan, Armando, composer. Introduction to Skin Anatomy and Physiology. 2019.

“Histology, Dermis.” National Library of Medicine, www.ncbi.nlm.nih.gov/books/NBK535346/#:~:text=The%20dermis%20is%20divided%20into,tissue%20that%20is%20highly%20vascular. Accessed 18 Oct. 2024.”In brief: How does skin work?” National Library of Medicine, www.ncbi.nlm.nih.gov/books/NBK279255/. Accessed 18 Oct. 2024.

The concept of shampooing your hair is profoundly ambiguous across social media. In the Western world, many people believe in the “no-poo” theory, claiming that terminating the use of shampoo will eventually train the scalp to regulate sebum production, resulting in healthier hair/scalp. This trend promotes using only water on the scalp, or the use of natural ingredients like baking soda and apple cider vinegar to cleanse the scalp instead of complex, synthetic chemical shampoo formulations. Despite the negative connotation of the word “chemicals,” a quality shampoo is essential in maintaining a healthy scalp/hair, which could not be achieved from the no-shampoo method.

Can you actually train your scalp’s sebum production?

Sebum is an essential natural oil your scalp produces that works to moisturize the hair and scalp. However, over time this sebum will continue to build up if a shampoo with oil-soluble compounds like sulfates, ceramides, or stearyl and cetyl alcohols isn’t used. Consequently, using only water will not dissolve sebum buildup, which could lead to dandruff and hair loss due to clogged hair follicles. In all, there is no scientific evidence that supports the theory of training your scalp and hair; you need to use shampoo to get rid of excess sebum and buildup to promote a healthy scalp. If you have curly/coily hair that is prone to frizz, simply limit the frequency of washing your hair rather than terminating shampoo completely. Training the scalp and hair is a myth.

Can you replace shampoo?

Baking soda, apple cider vinegar, and co-washing are a few popular alternatives for shampoo; but are they effective enough? 

Baking soda: Otherwise known as sodium bicarbonate, baking soda has a high pH level of 9. The scalp’s pH level is roughly 5.5, so using baking soda would likely cause irritation and damage to the hair cuticles. Shampoos, however, are typically formulated with a pH level between 3.5 – and 5.5, and gentle surfactants, making baking soda a poor alternative for shampoo.

Apple cider vinegar: 

CH3COOH, or apple cider vinegar, contains 5% acetic acid that works to gently fight bacteria and buildup on the scalp. Apple cider vinegar’s mildly acidic formula with a pH level of 2-3 makes it a more gentle alternative to shampoo. But is it still effective enough? Sebum on the scalp is mildly acidic with a pH level of 4.5 – 6, meaning that apple cider vinegar alone isn’t potent enough to counteract and control excess sebum. This pH imbalance can cause scalp issues.

Co-washing: 

Co-washing is the act of using a cleansing conditioner that is formulated to be massaged onto the scalp, simultaneously cleaning and moisturizing the hair/scalp This method is less stripping than shampoos, making it particularly useful for curly/coily hair because of their higher porosity and prone to breakage; straight and wavy hair may find that co-washing weighs down their hair strands.

Shampoo is necessary for healthy hair

Despite common misconception, shampoo isn’t bad for the hair as long as you’re using a quality, natural product that isn’t too drying. Shampoos are the safest and most effective way of cleansing the scalp and hair. Having healthy hair starts from the scalp, as the scalp gradually builds up sweat, sebum, and pollution that will start to clog the hair follicles. A scalp that isn’t sufficiently cleansed leads to inflammation and hair loss, whereas a healthy scalp can freely promote healthy hair growth. 

Works Cited

“Hair and Scalp Build-Up? What Can Help?” Chagrin Valley Soap & Salve Company, www.chagrinvalleysoapandsalve.com/blogs/idas-soap-box-blog/hair-and-scalp-build-up-what-can-help. Accessed 30 Sept. 2024.

“I Tried Oil Training My Hair, Here’s What Happened.” L’Oreal Paris, www.lorealparisusa.com/beauty-magazine/hair-care/thin-hair/editor-tries-oil-training-hair. Accessed 27 Sept. 2024.

“Sebum Build-Up on Scalp + How to Deal with It.” Taliah Waajid, 30 Aug. 2022, naturalhair.org/blogs/news/sebum-build-up-on-scalp-how-to-deal-with-it?srsltid=AfmBOopQhlcfSzAVFw8a-vEP–r9quoOgv99DRhjeytTI9UDTWc-3tfq. Accessed 27 Sept. 2024.

“The Shampoo pH can Affect the Hair: Myth or Reality?” National Library of Medicine, www.ncbi.nlm.nih.gov/pmc/articles/PMC4158629/#:~:text=The%20scalp%20pH%20is%205.5,effect.%5B12%2C17%5D. Accessed 30 Sept. 2024.”The Ultimate Guide To Hair pH.” Hair Know How, www.hairknowhow.com/ultimate-haircare-ph-guide. Accessed 27 Sept. 2024.

Introducing an exfoliating acid can result in a brighter, smoother skin complexion, but can be dangerous if done improperly. There are a variety of exfoliating acids that are tailored for each skin type, so here’s how to choose the right one:

Dry Skin

AHAs (alpha-hydroxy-acids) are a gentle, water-soluble exfoliant that is ideal for dry skin types. Both AHA’s and PHA’s are water-soluble exfoliants, but AHA’s are a bit smaller than PHA’s, allowing them to penetrate deeper into the skin, and thus exfoliate more effectively. Dry skin types should avoid BHA’s, because these exfoliants will penetrate too deep into the skin, extracting the skin’s much-needed sebum. I recommend using either mandelic acid or lactic acid instead of glycolic acid because of its deep penetration and risk of irritation.

Oily Skin

BHAs (beta-hydroxy-acids) are ideal for oily skin, as they are smaller, oil-soluble molecules, and thus can penetrate deeper into the skin. Not only will this treat open/large pores, but also help control sebum – unlike AHA’s and PHA’s. This makes BHA’s the optimal exfoliating acid for oily skin, but this group of acids is most likely to cause purging. If your oily skin can’t tolerate BHA’s, you can opt for glycolic acid, which is more gentle than something like salicylic acid since it is an AHA. It’s important to consider that AHA’s are not oil-soluble, meaning that they won’t help manage sebum, so you’ll likely need some other treatment as well.

Combination Skin

For combination skin, it’s best to avoid using a BHA for your entire face, as the dry parts of your face will likely flake because the BHA will penetrate too deep and extract too much moisture. To combat this issue, you can use an AHA/PHA – ideally PHA for sensitive skin – for the u-zone of the face, and a BHA for the oily t-zone. Alternatively, you can use an AHA/PHA for your entire face, incorporating niacinamide to control excess oil in the t-zone. Niacinamide is a vitamin that works to control excess sebum similar to a BHA, although it is less potent as it is not an exfoliating acid. Opt for niacinamide in the form of a serum, or infused in a moisturizer with at least 2% concentration. If you choose to use one exfoliating acid for dry-combination skin, I recommend the alpha-hydroxy-acid, lactic, as it is effective yet gentle. With the potency of this acid, it will effectively exfoliate the open pores/blackheads of your t-zone. While lactic acid is still an AHA, it is water-soluble and relatively large, meaning that it shouldn’t exacerbate the dry areas of your face. If your skin is insensitive, normal-combination, it may be able to tolerate glycolic acid without irritation.

Sensitive Skin

Whether you have dry, normal, combination, or oily skin, if your skin is also sensitive there isn’t a definitive answer to how you should exfoliate, since factors like the degree of skin sensitivity and sebum production come into play. In general, PHA’s are the safest option for sensitive skin, as these molecules are the largest of all exfoliating acids, making them safe for everyday use. PHA’s don’t penetrate the skin as deeply as BHA’s or AHA’s, so it often takes a lot longer for them to yield results. PHA’s are optimal for very sensitive skin types that can’t handle the penetration of AHA’s and BHA’s. However, a counterargument to this group of acids is that they aren’t oil-soluble, meaning they can’t manage sebum production. If you struggle with oily, sensitive skin, you can solve this issue by incorporating a low concentration of niacinamide into your routine. Some people with sensitive skin may be able to tolerate AHA’s/BHA’s, but as a general guideline to be safe, PHA’s are optimal for sensitive skin.

While exfoliating acids are not completely necessary in a solid skincare regimen, if you struggle with blackheads, texture, or hyperpigmentation, exfoliating can be the next step in reaching your skin goals.

Works Cited

“AHA and BHA Acids for the Skin: What’s the Difference?” Irvine Laser Center, www.irvinelasercenter.com/blog/aha-and-bha-acids-for-the-skin-whats-the-difference#:~:text=Solubility%3A%20AHA’s%20are%20water%20soluble,surface%20AND%20inside%20the%20pores. Accessed 7 Sept. 2024.

Best of The Ordinary | DOCTORLY Favorites. Produced by Muneeb Shah and Luke Maxfield.

“Unlocking the potential of niacinamide: What percentage is effective for skin health?” Curology, 31 Aug. 2023, curology.com/blog/niacinamide/. Accessed 7 Sept. 2024.