1. Why Oily and Dry Skin Can Occur at the Same Time

1.1 Sebum and Stratum Corneum Moisture Originate from Different Systems

Sebum is produced by the sebaceous glands located alongside hair follicles. Mature sebocytes accumulate lipid droplets in their cytoplasm and subsequently release their contents through holocrine secretion. Sebum mainly contains triglycerides and their breakdown products, wax esters, squalene, and cholesterol-related substances.

The skin’s water-retention capacity is maintained primarily by the stratum corneum. The stratum corneum consists of corneocytes, intercellular lipids, and natural moisturizing factors:

① Corneocytes provide space for absorbing and retaining water;

② Ceramides, cholesterol, and free fatty acids form the intercellular lipid barrier;

③ Natural moisturizing factors such as amino acids, PCA, lactates, and urea bind water within corneocytes.

Sebum can lubricate the skin and contribute to the formation of the surface lipid film, but it cannot replace the intercellular lipids of the stratum corneum, nor does it directly reflect the water content of the stratum corneum.

Studies of acne-prone skin have shown that skin with active sebum production may still exhibit increased transepidermal water loss (TEWL) and alterations in the ceramide composition of the stratum corneum.

Therefore, visible oiliness and skin dryness can occur simultaneously:

Continued sebum secretion by the sebaceous glands + reduced water-retention capacity of the stratum corneum = an oily surface with a dehydrated stratum corneum.

1.2 Main Reasons Why the Skin Becomes Dry After Oil-Control Treatment

Cleansing agents and oil-absorbing powders mainly act on sebum that has already reached the skin surface. Higher concentrations of volatile lower alcohols, such as ethanol, may also increase dryness or irritation.

Surfactants remove sebum and dirt through emulsification. However, when cleansing is too aggressive or performed too frequently, surfactants may also extract free fatty acids, cholesterol, and some ceramides from the stratum corneum, disrupting the orderly arrangement of intercellular lipids. Once the stratum corneum barrier is impaired, the outward diffusion of water increases, making the skin more prone to tightness, flaking, and irritation.

At the same time, androgen-related and lipid-synthesis signals within the sebaceous glands do not stop simply because surface oil has been washed away. The temporary dry or matte sensation after cleansing results from a reduction in surface lipids and does not mean that the sebaceous glands have reduced their rate of production.

Several hours later, newly produced sebum reaches the skin surface again, while the stratum corneum may already have lost water because of excessive cleansing. This produces a state in which “oiliness returns while tightness remains.”

This type of dryness occurs because the oil-control approach focuses on lipid removal and oil absorption without simultaneously maintaining stratum corneum lipids and natural moisturizing factors.

2. Biological Pathways Involved in Excessive Sebum Production

2.1 The Testosterone–DHT–Androgen Receptor Pathway

Human sebaceous gland cells can express androgen receptors and are capable of locally metabolizing androgens. Type I 5α-reductase can be detected in sebocytes and can convert testosterone into dihydrotestosterone (DHT).

The reaction can be simplified as follows:

Testosterone + NADPH + H⁺

—5α-reductase→ DHT + NADP⁺

NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate and serves as the reducing coenzyme required for the reaction.

After binding to the androgen receptor, DHT can affect sebocyte proliferation, differentiation, and lipid metabolism-related states. Studies using cultured human sebocytes have shown that the effects of DHT on sebocyte proliferation vary according to anatomical site, with facial sebocytes showing a more pronounced response.

The complete pathway can be represented as follows:

Testosterone → Type I 5α-reductase → DHT → androgen receptor activation → changes in sebocyte proliferation, differentiation, and metabolism-related signaling → possible enhancement of sebaceous gland activity

Greater skin oiliness does not necessarily mean that blood testosterone levels are elevated. Actual differences may also arise from:

① Local 5α-reductase activity within the sebaceous glands;

② The sensitivity of sebocytes to DHT;

③ Androgen receptor expression and responsiveness;

④ The number, size, and basal metabolic activity of the sebaceous glands.

Therefore, excessive sebum production is related not only to hormone concentrations but also to the local responsiveness of the sebaceous glands to hormonal signals.

2.2 The IGF-1–PI3K/Akt–SREBP-1 Pathway

DHT is not the only regulatory signal involved in sebum production.

Insulin-like growth factor-1 (IGF-1) can activate the phosphoinositide 3-kinase/protein kinase B pathway, known as the PI3K/Akt pathway, and subsequently increase the expression of sterol regulatory element-binding protein-1 (SREBP-1).

SREBP-1 is a transcription factor that primarily regulates genes involved in the synthesis of fatty acids, triglycerides, and other lipids. Studies of human sebocytes have shown that IGF-1 can increase SREBP-1 expression through PI3K/Akt signaling and promote lipid synthesis in sebocytes.

This pathway can be simplified as follows:

IGF-1 → IGF-1 receptor → PI3K/Akt → increased SREBP-1 expression → increased lipid-synthesis-related enzymes → increased production of sebaceous lipids

Sebum secretion is jointly regulated by androgens, IGF-1, genetic factors, environmental temperature, inflammation, and the differentiation state of sebocytes. Zinc PCA is mainly associated with certain steps that may be influenced by zinc ions and does not cover all signaling pathways involved in sebum production.

3. Chemical Structure of Zinc PCA

3.1 Structural Characteristics of L-PCA

The chemical name of L-PCA is L-5-oxoproline. It is also known as L-pyroglutamic acid or L-pyrrolidone carboxylic acid and has the molecular formula C₅H₇NO₃.

Its simplified cyclic structure can be represented as:

Cyclic [—NH—C(=O)—CH₂—CH₂—CH(COOH)—]

L-PCA contains the following structural units:

1. Five-membered lactam ring

The amino group and carboxyl group undergo intramolecular cyclization to form a stable five-membered ring. The ring contains one amide nitrogen and one carbonyl group.

2. Carboxyl group

Under appropriate pH conditions, the carboxyl group can lose a proton and form a negatively charged carboxylate:

L-PCA—COOH ⇌ L-PCA—COO⁻ + H⁺

3. Multiple oxygen-containing groups

The carboxyl group, carboxylate, and lactam carbonyl are all highly polar. They can form ion–dipole interactions or hydrogen bonds with water molecules and can also participate in metal-ion coordination.

3.2 Coordination Structure of Zinc PCA

Zinc PCA is also known as zinc pidolate or zinc pyroglutamate. Its commonly used stoichiometric formula is:

Zn(C₅H₆NO₃)₂

Its commonly used stoichiometric composition can be regarded as one divalent zinc ion corresponding to two deprotonated L-PCA anions.

The coordination process can be simplified as follows:

2 L-PCA—COOH ⇌ 2 L-PCA—COO⁻ + 2 H⁺

Zn²⁺ + 2 L-PCA⁻ ⇌ Zn(L-PCA)₂

These two equations are intended to illustrate the acid–base equilibrium and coordination relationship. They do not indicate that only one fixed molecular species exists in an aqueous formulation.

In actual formulations, zinc PCA is affected by pH, water content, concentration, other electrolytes, and chelating agents, resulting in a dynamic equilibrium involving coordination, partial dissociation, and reassociation. The bioavailability and irritation potential of zinc ions are also related to this equilibrium.

4. How Zinc Ions May Participate in Sebum Regulation

4.1 In Vitro Inhibition of 5α-Reductase

Explanations of the oil-control mechanism of zinc PCA frequently refer to the in vitro inhibitory effect of zinc ions on 5α-reductase.

A 1988 ex vivo human skin study used zinc sulfate to evaluate 5α-reductase activity. The results showed that zinc at experimental concentrations of 3 mmol/L and 9 mmol/L significantly inhibited 5α-reductase, while near-complete inhibition could occur at higher concentrations. The authors also noted that these findings required further verification under in vivo human conditions.

The proposed mechanistic pathway is therefore:

Partial dissociation of zinc PCA under certain conditions → increased availability of Zn²⁺ → possible reduction in 5α-reductase activity → reduced conversion of testosterone to DHT → reduced DHT stimulation of androgen receptors → attenuation of sebum-production signaling

This mechanism has a biochemical basis, but it cannot be used to conclude directly that a specific zinc PCA product can produce the same degree of enzyme inhibition within human sebaceous glands.

The reasons include:

① The key experiment used zinc sulfate rather than zinc PCA;

② The study evaluated enzyme activity ex vivo;

③ The effective zinc concentrations used in the experiment are not equivalent to the concentrations added to skincare formulations;

④ The degree of zinc PCA dissociation on the skin surface and its delivery into hair follicles depend on the formulation;

⑤ It remains uncertain whether a product can reach the sebaceous glands and achieve an effective local concentration.

Some clinical studies of topical combination formulations containing zinc have observed reductions in sebum output. However, because these formulations also contained erythromycin and other ingredients, the independent effects of zinc or zinc PCA cannot be determined from these studies. Overall, the quality of evidence for topical zinc in acne treatment is limited, and findings are not entirely consistent across studies.

Zinc PCA is therefore more appropriately regarded as a mild sebum-regulating ingredient rather than a pharmaceutical-grade 5α-reductase inhibitor.

4.2 Differences Between the Oil-Control Effects of Zinc PCA and Oil-Absorbing Ingredients

Oil-absorbing powders primarily use porous structures to adsorb surface lipids. They act on the skin surface and can usually reduce visible shine relatively quickly.

Zinc PCA acts in a different manner:

① It does not primarily function by adsorbing large amounts of existing sebum;

② Zinc ions may influence enzymes and signaling pathways associated with sebum production;

③ Its effects are influenced by continued use, formulation-dependent release, and individual responses;

④ Its immediate reduction of visible oiliness is generally less direct than that of oil-absorbing powders.

Therefore, the main value of zinc PCA lies in its potential to regulate the process of sebum formation and the follicular microenvironment rather than rapidly removing surface sebum.

5. Effects of Zinc Ions on Inflammation and the Microbial Environment

5.1 Modulation of Inflammation

Sebaceous glands not only synthesize lipids but also participate in local immune responses. Sebocytes can express pattern-recognition receptors and respond to microbial components and inflammatory signals. Oxidized sebum components, follicular blockage, and microbial metabolites may further promote inflammation.

In vitro keratinocyte studies have shown that zinc sulfate treatment can reduce certain cellular activation markers, suggesting that zinc salts may have inflammation-modulating potential.

For acne-prone skin, the potential relevance of zinc ions may include:

Reduced excessive activation of keratinocytes and perifollicular cells → reduced release of certain inflammatory mediators → attenuation of perifollicular inflammation → reduced persistent interference of inflammation with keratinization and barrier function

These studies mainly demonstrate the anti-inflammatory potential of zinc ions and do not indicate that all concentrations or dosage forms of zinc PCA will produce the same effects.

5.2 Inhibition of Cutibacterium acnes

The bacterium previously known as Propionibacterium acnes is now called Cutibacterium acnes, abbreviated as C. acnes. It is a normal component of the skin and hair-follicle microbiota. Acne development is associated with specific bacterial strains, the sebum environment, follicular blockage, and host immune responses, rather than being determined solely by the number of bacteria present.

One in vitro study used zinc PCA as a reference zinc compound to evaluate the inhibitory effects of several zinc–amino acid complexes against C. acnes. The results showed that the minimum inhibitory concentration of zinc PCA against C. acnes ATCC 6919 was 175 mg/L, indicating that zinc PCA inhibited the growth of this strain under the experimental conditions.

The antibacterial effects of zinc compounds may involve:

① Interference by Zn²⁺ with normal bacterial enzyme function;

② Alteration of cell membrane permeability;

③ Disruption of energy metabolism and protein function;

④ Inhibition of bacterial growth at sufficient concentrations.

Zinc PCA may therefore be regarded as having the potential to modulate the follicular microbial environment rather than acting as a broad-spectrum disinfectant. In vitro antibacterial concentrations also cannot be directly equated with concentrations achieved during actual use on the skin or with clinical anti-acne efficacy.

6. How the L-PCA Structure in Zinc PCA May Support Stratum Corneum Hydration

6.1 Endogenous L-PCA Is a Component of the Natural Moisturizing Factor

Natural moisturizing factor (NMF) is a collective term for a group of low-molecular-weight, water-soluble substances present within corneocytes. Its main components include free amino acids, pyrrolidone carboxylic acid (PCA), lactates, urea, inorganic ions, and other small molecules.

During keratinocyte differentiation, filaggrin is gradually broken down into free amino acids and their derivatives, among which glutamine can be further converted into PCA. In dermatological literature, this endogenous component is generally referred to simply as PCA. From the perspective of its stereochemical origin, the naturally occurring PCA discussed in this article is primarily the L-isomer, or L-PCA. PCA levels in the stratum corneum are commonly used as an indicator of natural moisturizing factor status.

L-PCA contains hydrophilic groups, including a carboxyl or carboxylate group and a lactam carbonyl group. These groups can interact with water molecules through ion–dipole interactions and hydrogen bonding, helping corneocytes maintain hydration.

L-PCA differs from occlusive lipids in its moisturizing mechanism:

① L-PCA primarily helps corneocytes attract and bind water;

② Intercellular lipids primarily limit the outward diffusion of water;

③ Together, they help maintain the water content of the stratum corneum.

6.2 Relationship Between L-PCA and Normal Desquamation

Normal desquamation of the stratum corneum depends on the gradual degradation of the structures that connect corneocytes. The activity of proteases involved in this process is influenced by stratum corneum water content and pH.

Studies using human skin-equivalent models have shown that water distribution in the stratum corneum is associated with natural moisturizing factor content. Reduced PCA levels and insufficient stratum corneum hydration may alter the environment in which desquamation-related enzymes function.

The effects of zinc PCA on the condition of the stratum corneum can be represented as follows:

Hydrophilic structures associated with L-PCA → support for stratum corneum hydration → maintenance of corneocyte flexibility → provision of a suitable environment for normal desquamation

This effect represents support for stratum corneum hydration and differs from the exfoliating actions of salicylic acid, alpha-hydroxy acids, or retinoid-related ingredients. Zinc PCA cannot directly dissolve keratin plugs and is not a primary keratinization-regulating ingredient for treating closed comedones or blackheads.

6.3 L-PCA in Zinc PCA Differs from Endogenous Free PCA

PCA in the natural moisturizing factor of the stratum corneum is present mainly as the free acid and its carboxylate form. In zinc PCA, L-PCA is present as a deprotonated L-PCA anion coordinated with Zn²⁺. The two share the same L-pyroglutamic acid structural origin but exist in different chemical states.

In aqueous formulations and on the skin surface, zinc PCA may exist in a dynamic equilibrium involving coordination, partial dissociation, and reassociation. Zinc coordination species and a certain proportion of L-PCA anions may therefore coexist in the system. The PCA portion retains hydrophilic structures such as carboxylate and carbonyl groups. However, direct clinical evidence regarding the specific moisturizing effects of zinc PCA on human skin remains limited.

Zinc PCA is relatively unlikely to cause marked drying for two main reasons:

1. Its sebum-regulating action does not primarily rely on aggressive cleansing or the extensive adsorption of surface lipids;

2. Its L-PCA ligand has a hydrophilic structure and is theoretically compatible with moisturizing systems.

Zinc PCA cannot replace a complete moisturizing system. Water retention in the stratum corneum still requires humectants such as glycerol, amino acids, and urea, together with barrier lipids such as ceramides, cholesterol, and fatty acids, as well as an appropriate amount of emollients.

7. Overall Skincare Mechanisms of Zinc PCA

The effects of zinc PCA can be summarized as an interconnected pathway:

7.1 Sebum Regulation

Zn²⁺ may affect 5α-reductase → local DHT-related signaling may decline → some androgen-driven sebaceous activity may be reduced

This proposed effect is based mainly on in vitro studies of zinc salts. Its effects in human use depend on formulation characteristics and skin delivery.

7.2 Modulation of Inflammation and the Microbial Environment

Zn²⁺ may affect cellular activation and microbial metabolism → reduce certain inflammatory stimuli → limit excessive growth of C. acnes in a high-sebum environment → improve the follicular sebum–microorganism–inflammation cycle

This effect is supported by in vitro studies. Actual performance depends on zinc concentration, release state, and the duration of contact provided by the formulation.

7.3 Support for Stratum Corneum Hydration

Hydrophilic structures associated with L-PCA → interaction with water → improvement of the corneocyte hydration environment → support for normal flexibility and desquamation conditions

This effect may help reduce the likelihood of tightness caused by oil-control methods based solely on lipid removal, but it cannot independently repair a markedly damaged stratum corneum lipid barrier.

7.4 Effects on the Appearance of Pores

Zinc PCA cannot alter the fundamental anatomical structure of hair follicles, nor can it permanently reduce pore size.

When sebum production, surface shine, and perifollicular inflammation decrease, lipid accumulation and light reflection around the follicular opening may be reduced, making pores appear less visible.

The pathway can be represented as follows:

Reduced sebum and surface shine→

① Reduced accumulation around the follicular opening

② Reduced inflammatory swelling→ A smoother appearance of pores

This represents an improvement in the appearance of pores rather than a structural contraction of pore tissue.

8. Why Zinc PCA Alone Cannot Determine Whether a Product Will Cause Dryness

Zinc PCA has sebum-regulating properties and is compatible with moisturizing systems, but the final effects of a product are determined by the formulation as a whole.

The main factors influencing the degree of skin dryness include:

① The types and total concentrations of surfactants;

② The content of volatile alcohols;

③ The combined intensity of salicylic acid, alpha-hydroxy acids, and retinoid-related ingredients;

④ The inclusion of humectants such as glycerol, panthenol, betaine, and amino acids;

⑤ The inclusion of barrier lipids such as ceramides, cholesterol, and fatty acids;

⑥ Whether the product is rinse-off or leave-on;

⑦ The concentration of zinc PCA, the pH, and the release state of zinc ions.

In facial cleansers, zinc PCA remains in contact with the skin for only a short period, and post-use dryness is determined mainly by the cleansing system. In leave-on products such as serums, gels, and emulsions, zinc PCA has a longer contact time and is therefore more consistent with applications intended to regulate sebum, inflammation, and the follicular microenvironment.

The presence of zinc PCA in a formulation cannot offset the irritation caused by aggressive cleansing, high alcohol content, or the combined use of multiple exfoliating ingredients. Persistent tightness, flaking, stinging, and redness generally indicate that the overall skincare regimen has exceeded the skin’s tolerance.

9. Classification of Representative Chemicals Related to Zinc PCA–Mediated Sebum Regulation and Stratum Corneum Hydration

Table 1. PCA-System Ingredients Related to Stratum Corneum Hydration

Table 2. Zinc Sources and Ingredients Related to Sebum and Follicular Regulation

Table 3. Stratum Corneum Barrier Lipids and Fatty Acids

Table 4. Substances Used for Sebum-Composition Simulation, Lipid Analysis, and Biochemical Mechanism Research

Note: The products listed above are representative Aladdin products related to scientific and formulation research. The “Applications” listed in the tables are suggested research directions and do not indicate that the corresponding catalog products have been validated for those specific uses. Before conducting experiments, suitability should be assessed according to the product grade, purity, impurities, certificate of analysis (COA), solubility, and the requirements of the experimental system.

References

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