How Glycolic Acid Works on Skin

Glycolic acid is one of the most studied active ingredients in dermatology, but understanding how it works - not just what it does - is the key to using it effectively. Its mechanisms operate at multiple levels of the skin, from dissolving bonds between dead surface cells to stimulating the production of collagen and hyaluronic acid deep in the dermis. Critically, these effects depend on three interconnected variables: concentration, pH, and contact time [1].

Molecular Size: Why Glycolic Acid Penetrates Better

All alpha hydroxy acids (AHAs) share a common chemical structure: an organic acid with a hydroxyl group on the alpha carbon. How do alpha hydroxy acids work? They all exfoliate by disrupting bonds between dead skin cells, but their molecular size determines how deeply they penetrate. The AHA family includes lactic acid (90.08 Da), mandelic acid (152.15 Da), tartaric acid (150.09 Da), and citric acid (192.12 Da). Glycolic acid, at just 76.05 daltons, is the smallest member [2].

This size difference is not trivial. The stratum corneum (the outermost layer of skin) acts as a barrier composed of dead corneocytes embedded in a lipid matrix, sometimes described as a "bricks and mortar" structure. For any molecule to penetrate this barrier and exert a biological effect, it must be small enough to pass through the intercellular spaces. Glycolic acid's low molecular weight allows it to penetrate more rapidly and deeply than larger AHAs, which is why it generally produces more noticeable results at equivalent concentrations [1].

This deeper penetration is a double-edged sword. It means glycolic acid is more effective, but it also carries a higher risk of irritation compared to gentler alternatives like mandelic or lactic acid, particularly for people with sensitive skin or compromised barriers. If you are new to glycolic acid, see our beginner's guide to using glycolic acid for how to start safely.

Surface Exfoliation: Corneodesmolysis

The most immediate and visible effect of glycolic acid occurs in the epidermis, specifically in the stratum corneum.

How Dead Skin Cells Are Held Together

The stratum corneum is composed of approximately 15–20 layers of dead, flattened corneocytes. These cells are held together by protein structures called corneodesmosomes, modified desmosomal junctions that provide mechanical cohesion to the outermost skin layer. Under normal conditions, enzymes in the skin gradually break down these junctions from the surface outward, allowing dead cells to shed naturally through a process called desquamation [1].

With age, sun damage, and certain skin conditions, this desquamation process slows. Dead cells accumulate on the surface, leading to dullness, rough texture, uneven tone, and clogged pores.

How Glycolic Acid Dissolves These Bonds

Glycolic acid accelerates desquamation by chemically disrupting corneodesmosomes, a process called corneodesmolysis. A landmark ultrastructural study by Fartasch, Teal, and Menon (1997) used electron microscopy to examine human skin treated with 4% glycolic acid over three weeks. They found that glycolic acid caused targeted desmosomal breakdown in the stratum disjunctum (the outermost, loosely attached layers of dead cells) while leaving the stratum compactum (the deeper, tightly packed layers) intact [3].

Critically, this study also measured transepidermal water loss (TEWL), a marker of barrier integrity, and found no increase. This means that at appropriate concentrations, glycolic acid exfoliates without compromising the skin barrier [3].

The result of corneodesmolysis is smoother, more even-toned skin. By clearing the buildup of dead cells, glycolic acid also helps prevent the clogged pores that lead to comedonal acne, and it allows other skincare products to penetrate more effectively.

Dermal Stimulation: Collagen, Hyaluronic Acid, and Fibroblasts

Glycolic acid does not stop at the surface. At sufficient concentrations and low pH, it penetrates into the dermis and triggers biological responses in fibroblasts, the cells responsible for producing the structural proteins that keep skin firm and hydrated.

Collagen Synthesis

In a vehicle-controlled human study, Bernstein et al. (2001) applied 20% glycolic acid lotion to forearm skin twice daily for three months. They found significant increases in type I collagen mRNA and hyaluronic acid content in both the epidermis and dermis compared to the vehicle-treated control [4]. Type I collagen is the primary structural protein in skin, and its degradation is a hallmark of aging.

Separate in vitro studies by Kim et al. (1998) and Moy, Howe, and Moy (1996) confirmed that glycolic acid directly stimulates fibroblast proliferation and collagen production in a dose-dependent manner [5] [6]. Okano et al. (2003) further demonstrated that glycolic acid promotes collagen synthesis through two pathways: directly via fibroblasts, and indirectly through cytokines released by keratinocytes in the epidermis [7].

Hyaluronic Acid Production

The same Bernstein study showed that glycolic acid treatment significantly increased hyaluronic acid (HA) content in human skin [4]. Hyaluronic acid is a glycosaminoglycan that binds water (up to 1,000 times its weight), making it essential for skin hydration, plumpness, and volume. The decline of hyaluronic acid in the dermis is one reason skin becomes drier and thinner with age.

By stimulating HA production, glycolic acid contributes to improved skin hydration from within, complementing its surface-level exfoliating effects.

Epidermal Renewal via TRPV1 Activation

A study by Kim and Won (2010) identified a specific molecular mechanism by which glycolic acid stimulates epidermal renewal. Using a reconstructed skin equivalent model, they found that glycolic acid activates TRPV1, a pH-sensitive ion channel on keratinocytes, triggering increased keratinocyte proliferation. This effect was pH-dependent and could be blocked by TRPV1 antagonists [8].

This finding provides a molecular explanation for the clinical observation that glycolic acid accelerates cell turnover: it is not merely removing dead cells from the surface but also signaling the living epidermis to produce new cells faster.

The Role of pH: Why It Determines Everything

Understanding pH is arguably the most important piece of glycolic acid science for consumers. For a deeper dive into how acidity affects skincare formulations, see our guide to the science of pH in skincare. Two products can both claim "10% glycolic acid" on the label, but if one is formulated at pH 3.0 and the other at pH 4.5, they will deliver dramatically different amounts of active acid to the skin.

Free Acid vs. Dissociated Glycolate

Glycolic acid (HOCH2COOH) is a weak acid with a pKa of 3.83. In solution, it exists in equilibrium between two forms:

• Free acid (protonated form, HA): This is the biologically active form. It is uncharged, which allows it to penetrate the lipid-rich stratum corneum.
• Glycolate ion (dissociated form, A-): This is the ionized, negatively charged form. It cannot easily cross the skin barrier and has minimal exfoliating activity.

The ratio between these two forms is determined entirely by the pH of the product relative to the pKa [2].

The Henderson-Hasselbalch Equation

The relationship between pH, pKa, and the percentage of active free acid follows the Henderson-Hasselbalch equation:

pH = pKa + log([A-]/[HA])

For glycolic acid (pKa = 3.83), this translates to the following approximate free acid percentages at different pH values [9]:

| Product pH | % Free Acid | What This Means | |-----------|-------------|-----------------| | 2.0 | ~98.5% | Almost entirely active. Very aggressive; professional peel territory. | | 3.0 | ~87% | Highly active. Effective but potentially irritating for daily use. | | 3.5 | ~68% | Strong activity. Typical of well-formulated leave-on treatments. | | 3.83 | 50% | Exactly half active, half ionized. The pKa point. | | 4.0 | ~41% | Moderate activity. Many consumer products sit here. | | 4.5 | ~18% | Low activity. Gentle, minimal exfoliation. | | 6.0 | ~0.67% | Essentially inactive for exfoliation. |

This means a "10% glycolic acid" product at pH 3.5 delivers approximately 6.8% free acid, while the same product reformulated at pH 4.5 delivers only about 1.8% free acid. The label percentage is the same, but the effective dose is nearly four times different.

What This Means for Product Selection

The pH-concentration relationship explains several things that confuse consumers:

• Why some "low-percentage" products feel stronger than "high-percentage" ones. A 5% glycolic acid product at pH 3.0 (free acid: ~4.35%) can feel more active than a 10% product at pH 4.5 (free acid: ~1.8%).
• Why "partially neutralized" products exist. Some brands adjust (raise) the pH of their glycolic acid formulations to reduce irritation while maintaining some activity. Narda et al. (2021) demonstrated that glycolic acid at pH 4 still stimulates collagen production and desquamation without increasing the pro-inflammatory marker TNF-alpha [10].
• Why the Edraki et al. (2022) RCT found that a 5% glycolic acid complex outperformed 20% glycolic acid for acne. The lower-concentration product was likely better formulated, with a more effective free acid value for its intended purpose 11.

Regulatory Standards

Regulatory bodies set both concentration and pH limits for consumer products:

| Standard | Max Concentration | Min pH | |---------|------------------|--------| | CIR (US) | 10% | 3.5 | | SCCS (EU) | 4% | 3.8 |

The EU is significantly more restrictive than the US. Products exceeding these limits are restricted to professional use in Europe 12 13.

Cell Turnover Acceleration

The combined effect of surface exfoliation (corneodesmolysis) and epidermal renewal (TRPV1-mediated keratinocyte proliferation) produces an overall acceleration of the skin's natural cell turnover cycle.

In young adults, epidermal turnover (the time it takes for a new keratinocyte born in the basal layer to reach the surface and be shed) is approximately 28 days. This slows to 40–60 days with age, contributing to dullness, uneven pigmentation, and slower wound healing.

Glycolic acid helps return this cycle closer to its youthful pace. This accelerated turnover is responsible for many of the visible benefits users notice:

• Smoother texture - fresh cells replace the accumulated dead layer more quickly
• Faded dark spots - melanin-containing cells are shed faster, dispersing pigment deposits. Usuki et al. (2003) demonstrated that glycolic acid also directly inhibits tyrosinase activity, reducing melanin synthesis 14.
• Improved radiance - the thinner, more uniform dead cell layer reflects light more evenly
• Better product absorption - fewer layers of dead cells means active ingredients from other products penetrate more effectively

For a detailed breakdown of each benefit with the supporting evidence, see our glycolic acid benefits guide.

The Dose-Response Relationship

Glycolic acid is fundamentally dose-dependent, but the "dose" is not simply the percentage on the label. The effective dose is a function of three interacting variables. Our concentration guide explains how to apply these principles when selecting a product:

1. Concentration

Higher concentrations deliver more glycolic acid molecules to the skin. Clinical studies have tested concentrations ranging from 2% (gentle daily use) to 70% (professional peels). The effects scale with concentration: Moy et al. (1996) showed dose-dependent collagen stimulation in fibroblast cultures 6, and histological studies by Moy et al. (1996) demonstrated that 70% peels cause more tissue necrosis than 50% peels 15.

2. pH (Free Acid Value)

As discussed above, pH determines what fraction of the nominal concentration is biologically active. The effective dose is best understood as the free acid value: the product of concentration and the percentage of undissociated acid at the product's pH.

3. Contact Time

A glycolic acid cleanser that is rinsed off after 30 seconds delivers far less active acid to the skin than a leave-on serum at the same concentration and pH. Professional peels are typically left on for 1–5 minutes before neutralization, with the application time calibrated to the desired depth of penetration and the patient's skin response [1].

These three variables interact to determine the total "acid exposure" of a treatment. This is why a 5% glycolic acid serum used nightly (leave-on, moderate pH, long contact) can produce results comparable to a weekly 30% peel (high concentration, low pH, short contact).

Putting It All Together

The science of glycolic acid can be summarized as a multi-level process:

1. Glycolic acid's small molecular size (76.05 Da) allows it to penetrate the stratum corneum faster and deeper than other AHAs.
2. At the surface, it disrupts corneodesmosomes through corneodesmolysis, accelerating the shedding of dead cells without compromising barrier function 3.
3. In the epidermis, it activates TRPV1 channels on keratinocytes, signaling increased cell proliferation 8.
4. In the dermis, it stimulates fibroblasts to produce more type I collagen and hyaluronic acid 4.
5. The degree of all these effects depends on the interplay of concentration, pH (free acid value), and contact time.

Understanding these mechanisms helps explain not just what glycolic acid does, but why proper formulation, gradual introduction, and sunscreen use are essential for safe and effective results. For information on potential side effects and how to minimize them, see our side effects and safety guide.

References

1. Sharad J. "Glycolic acid peel therapy - a current review." Clin Cosmet Investig Dermatol. 2013;6:281-288. doi:10.2147/CCID.S34029
2. Tang SC, Yang JH. "Dual Effects of Alpha-Hydroxy Acids on the Skin." Molecules. 2018;23(4):863. doi:10.3390/molecules23040863
3. Fartasch M, Teal J, Menon GK. "Mode of action of glycolic acid on human stratum corneum: ultrastructural and functional evaluation of the epidermal barrier." Arch Dermatol Res. 1997;289(7):404-409. doi:10.1007/s004030050212
4. Bernstein EF, Lee J, Brown DB, et al. "Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin." Dermatol Surg. 2001;27(5):429-433. doi:10.1046/j.1524-4725.2001.00234.x
5. Kim SJ, Park JH, Kim DH, Won YH, Maibach HI. "Increased in vivo collagen synthesis and in vitro cell proliferative effect of glycolic acid." Dermatol Surg. 1998;24(10):1054-1058.
6. Moy LS, Howe K, Moy RL. "Glycolic acid modulation of collagen production in human skin fibroblast cultures in vitro." Dermatol Surg. 1996;22(5):439-441.
7. Okano Y, Abe Y, Masaki H, et al. "Biological effects of glycolic acid on dermal matrix metabolism mediated by dermal fibroblasts and epidermal keratinocytes." Exp Dermatol. 2003;12 Suppl 2:57-63.
8. Kim SJ, Won YH. "Glycolic acid induces keratinocyte proliferation in a skin equivalent model via TRPV1 activation." J Dermatol Sci. 2010;57(3):197-199. doi:10.1016/j.jdermsci.2009.12.004
9. Henderson-Hasselbalch equation applied to glycolic acid (pKa 3.83). See: Green BA, Yu RJ, Van Scott EJ. "Clinical and cosmeceutical uses of hydroxyacids." Clin Dermatol. 2009;27(5):495-501.
10. Narda M, Trullas C, Brown A, et al. "Glycolic acid adjusted to pH 4 stimulates collagen production and epidermal renewal without affecting levels of proinflammatory TNF-alpha in human skin explants." J Cosmet Dermatol. 2021;20(2):513-521. doi:10.1111/jocd.13570
11. Edraki K, et al. "Effect of 5% glycolic acid complex and 20% glycolic acid on mild-to-moderate facial acne vulgaris." Chin Med J (Engl). 2022;135(21):2608-2614.
12. Andersen FA. "Final Report on the Safety Assessment of Glycolic Acid..." Int J Toxicol. 1998;17(Suppl 1):1-241. doi:10.1177/109158189801700101
13. Scientific Committee on Consumer Safety (SCCS). Opinion on Alpha-Hydroxy Acids. SCCNFP/0370/00. 2000.
14. Usuki A, Ohashi A, Sato H, et al. "The inhibitory effect of glycolic acid and lactic acid on melanin synthesis in melanoma cells." Exp Dermatol. 2003;12 Suppl 2:43-50.
15. Moy RL, et al. "A histological comparison of 50% and 70% glycolic acid peels using solutions with various pHs." Dermatol Surg. 1996;22(5):463-465.
16. American Academy of Dermatology. "Chemical Peels." Patient education resource. aad.org

---

This article is for informational purposes only and does not constitute medical advice. Consult a board-certified dermatologist before starting any new skincare treatment.