AHAs: Glycolic, Lactic, Mandelic

The three workhorse alpha-hydroxy acids — glycolic, lactic and mandelic — share one mechanism but behave very differently at the chair, and the variable that separates them is mostly molecular size. Glycolic is the smallest molecule, so it penetrates fastest and deepest and irritates most; mandelic is the largest, so it penetrates slowly and evenly with the least inflammation; lactic sits between them and adds a humectant quality. Choosing the right AHA is therefore a question of matching penetration kinetics to the indication and — critically in melanin-rich skin — to how much inflammation the patient can tolerate without tipping into post-inflammatory hyperpigmentation (PIH).

One mechanism, three molecules

All AHAs are water-soluble carboxylic acids that work by reducing corneocyte cohesion in the lower stratum corneum, triggering controlled desquamation and accelerating epidermal turnover. At higher concentrations and lower pH they reach into the epidermis and can stimulate dermal remodelling over a series. Because they are hydrophilic, they engage the surface broadly rather than seeking out the follicle — which is the key contrast with lipophilic salicylic acid (covered in the next lesson).

Two formulation variables govern how much of that mechanism is expressed:

• Free-acid value and pH. The proportion of acid in its protonated, un-ionised (active) form rises as pH falls below the acid's pKa (glycolic and lactic both ≈3.8, mandelic ≈3.4). A glycolic at pH 2 is a far more aggressive peel than the same percentage buffered to pH 4 — which is exactly why label percentage alone never predicts potency (the subject of the final lesson in this module).
• Contact time. Because AHAs are not self-neutralising, time-on-skin is the dose dial. The peel runs until you neutralise it, so contact time is as much a part of the dose as concentration.

Glycolic acid — small, fast, potent

Glycolic acid (≈76 Da) is the smallest AHA, and its small size is the source of both its strength and its risk. It penetrates the stratum corneum fast and relatively deeply, making it the most efficient AHA for genuine resurfacing of dullness, fine lines, uneven tone and texture. But fast penetration is also uneven penetration — it bites harder where the barrier is thin or stripped — and it carries the highest irritation and PIH potential of the three.

In practice glycolic is the AHA you reach for when you want metabolic punch and the patient has demonstrated tolerance: lighter phototypes, primed skin, or a darker-skinned patient who has already cleared lower-risk peels in a series. It is titratable across a wide strength ladder (20–70%), and at the highest strengths it demands disciplined timing and ready neutralisation.

Lactic acid — the hydrating mid-size AHA

Lactic acid (≈90 Da) is larger and slower than glycolic and carries a useful second property: it is a component of the skin's natural moisturising factor, so it is humectant and barrier-friendly as well as keratolytic. That makes it the AHA of choice for dry, sensitive or barrier-compromised skin, and for patients who flare on glycolic. It does real work on tone, fine texture and mild pigment while running gentler, and it pairs well in combination peels (it is one of the three acids in Jessner's solution).

Mandelic acid — large, slow, even

Mandelic acid (≈152 Da) is by far the largest of the three, and its size makes it the gentlest and most even AHA. It diffuses slowly and uniformly across oily and dry zones alike, producing a low-irritation superficial peel — the property that makes it the most defensible first peel in Fitzpatrick IV–VI skin, where inflammation is the upstream trigger of PIH. It also has mild antibacterial activity useful in comedonal and inflammatory acne. The trade-off is that it does less per session than glycolic; mandelic builds results across a series rather than in one aggressive pass.

Choosing by indication and phototype

The skin-of-color logic is the through-line: in Fitzpatrick IV–VI you start with the largest, slowest molecule (mandelic), use lactic when the barrier needs humectant support, and reserve glycolic — and especially high-strength glycolic — for skin that has earned it across a series. Visible peeling is not the goal; an even, low-inflammation endpoint is.

Key takeaway

Glycolic, lactic and mandelic are one mechanism in three molecular sizes. Glycolic is small, fast and potent but the most irritating and PIH-prone; lactic is mid-size, humectant and gentle; mandelic is large, slow, even and the safest in darker skin. Choose by matching penetration kinetics to the indication and the patient's tolerance — start large and slow in Fitzpatrick IV–VI, escalate to small and fast only once tolerance is proven, and remember that pH and contact time, not label percentage, set the real dose.