Glycolic Acid

Glycolic acid is a natural organic acid derived from sugar cane. A popular exfoliant, it provides benefits in clearing up acne, reducing fine lines and wrinkles, and much more.

Effects


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments

A

Wrinkle treatment

Moderate

Glycolic acid peels ameliorate fine lines and wrinkles but are less effective on deep wrinkles. Glycolic acid creams are less effective than peels.

A

Skin lightening

Moderate

Improves skin colour and radiance, and reduces pigmentation, solar lentigines and facial dyschromia.

B

Smoother skin

Moderate

Improves the texture of the skin in both healthy individuals and acne patients.

B

Increased skin thickness

Moderate

Restores the thickness of the skin, increasing epidermal thickness by 27% in 6 months.

B

Reduced actinic keratoses

Mild

Decreases the number of actinic keratoses, but is more effective when used in conjunction with 5-fluorouracil.

C

Less visible scars

Strong

Glycolic acid peels Improve post-acne superficial scarring.

C

Acne treatment

Moderate

Useful as an adjunctive treamtent for acne, and also helps reduce acne scars and post-inflammatory hyperpigmentation.

C

Melasma treatment

Moderate

Treats melasma by suppressing melanin production in melanocytes.

C

Increased skin hydration

Mild

Improves the moisture content of the skin, but to a smaller extent than lactic acid.

C

Increased skin elasticity

Mild

Less effective than tretinoin in improving skin elasticity in post-menopausal women.

D

Smaller pores

Moderate

Reduces pore size in acne patients and when used together with vitamin C cream and exposure to a dual-wavelength system of light.

D

Antioxidant

Mild

May enhance the penetration and availability of antioxidants to the epidermis.

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Scientific Research


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Table of contents:

1. Sources

Glycolic acid is a natural α-hydroxy acid found in many plants, especially sugar cane.[1] However, most glycolic acid in use today are chemically synthesized.

2. Bioavailability

Glycolic acid peels are commercially available as free acids, partially neutralized, buffered or esterified solutions in concentrations ranging from 20% to as high as 70%.[2]

Glycolic has the lowest molecular weight amongst all α-hydroxy acids. As such, it penetrates the skin easily.[2] 24 hours after 4% glycolic acid was applied to human skin specimens, 2.7% of the applied dose was found in the stratum corneum and 13.5% in the viable skin.[3]

In general, gel formulations of glycolic acid penetrate more slowly.[4] Absorption is also pH, strength and time-dependent. In fact, the depth of penetration relies on the duration of acid application.[5] Decreasing the skin's pH also increases its permeability.[6]

3. Effects on the skin

3.1 Anti-wrinkle effect

Glycolic acid has been used extensively for the treatment of wrinkles. An early pilot study found that monthly superficial peels with 70% glycolic acid provided improvements in fine wrinkling when used concomitantly with a 10% glycolic acid-based moisturizer twice daily.[7] A double-blind, vehicle-controlled study that same year showed that 50% glycolic acid applied for 5 minutes to the face, once weekly for 4 weeks, decreased fine wrinkling.[8] Computer-assisted image analysis have also revealed that glycolic acid peeling changes both wrinkle length and the number of wrinkles.[9] More recently, 70% glycolic acid peels were observed to be effective in reducing fine wrinkles on the external-lateral region of the eyes after 3 applications.[10] 20% to 50% glycolic acid peels also improved fine lines and wrinkles in 30% of subjects when used at biweekly intervals for 12 weeks.[11]

However, superficial glycolic acid peels do not seem to improve wrinkles in those aged above 70.[9] This may be because their wrinkles are mostly coarse rather than fine wrinkles.[12] If glycolic acid peeling with 70% free acid remains in contact with the skin for 15 minutes, this has a similar effect to a medium peeling of 40% trichloroacetic acid, enabling action on deeper wrinkles, but there is a risk of hyperpigmentation, as glycolic acid increases the dispersion of melanin granules through the epidermis.[13]

Glycolic acid creams do not appear to be as effective as peels in effacing wrinkles. 5% glycolic acid cream did not reduce wrinkles on the face and neck to a significant extent in one double-blind, placebo-controlled trial.[14]

Topical vitamin C + glycolic acid peels did not improve wrinkles, but the addition of exposure to intense light, specifically a nonthermal blue (405- to 420-nm) and near-infrared light (850- to 900-nm) dual-wavelength system, led to a significant improvement in rhytids.[15]

Numerous in-vitro studies have shown that glycolic acid elevates collagen production and cell proliferation in human fibroblasts.[16][17][18] It also increases the hyaluronic acid content of human skin.[19]

3.2 Increased antioxidant activity

There is some evidence that glycolic acid can potentiate the antioxidant action of vitamin E and melatonin, suggesting that combining glycolic acid with these antioxidants can improve the penetration and availability of antioxidants to the epidermis and enhance their protective potential.[20]

3.3 Improved texture

One study has demonstrated that applying 5% glycolic acid cream to the face and neck for 3 months led to a statistically significant improvement in general skin texture.[14] A similar result was found when acne patients were treated with 35% and 50% glycolic acid peels once in 3 weeks for 10 weeks.[21]

3.4 Lightening effect

Short contact therapy with 70% glycolic acid on a monthly basis, plus treatment with a 10% glycolic acid-base moisturizer twice daily was found to improved pigmentation, though only to a slight extent.[7] 20% to 50% glycolic acid peel also reduced hyperpigmentation, but in a smaller proportion of subjects compared to capryloyl salicyclic acid peel.[11]

Glycolic acid peels have also been shown to lighten solar lentigines,[8] and to lead to more radiant skin when combined with vitamin C cream.[15]

Moreover, topical 5% and 8% glycolic acid creams have been demonstrated to improve skin discoloration and skin sallowness respectively.[14][22]

A formulation containing glycolic acid, kojic acid and emblica extract also appears to be a good alternative to 4% hydroquinone in treating mild to moderate facial dyschromia.[23]

3.5 Increased thickness

6 months treatment with 15% glycolic acid cream successfully reversed epidermal and dermal markers of skin aging, including rete peg pattern and epidermal thickness. Specifically, a 27% increase in epidermal thickness was seen.[24]

2 separate studies have conducted histologic examinations of skin treated with 50% glycolic acid. One revealed a thinning of the stratum corneum, an enhancement of the granular layer, epidermal thicknening and in some cases, an increase in collagen thickness in the dermis.[8] In the other study, the epidermis of glycolic acid-treated skin, excluding the stratum corneum, was 105.2µm, in contrast to the 70.0µm of untreated skin.[25]

3.6 Increased hydration

One study showed that a combined retinol-lactose-glycolic acid cream significantly improved moisturization compared with baseline and control.[26] However, glycolic acid appears to be less effective than lactic acid in improving skin hydration.[27]

3.7 Improved elasticity

A double-blind study comparing 0.05% tretinoin and 6% glycolic acid found that skin elasticity in menopausal women was significantly higher following tretinoin treatment than glycolic acid treatment.[28]

3.8 Reduced pore size

One study showed that the combination of topical vitamin C, glycolic acid peels and skin exposure to a dual wavelength system consisting of nonthermal blue (405- to 420-nm) and near-infrared light, significantly improved pore size.[15] Glycolic acid peels also reduced follicular pore size in Asian patients with acne.[21]

3.9 Reduced actinic keratoses

In one study, 50% glycolic acid applied on a weekly basis for 4 weeks resulted in fewer actinic keratoses.[8] 70% glycolic acid applied simultaneously with 35% trichloroacetic acid is also a good medium-depth peel,[29] and is more effective than Jessner's solution in removing actinic keratoses.[30]

Combining glycolic acid with 5-fluorouracil is both more effective than glycolic acid alone, and shortens the healing time.[31]

3.10 Acne vulgaris treatment

Glycolic acid peeling is useful as an adjunctive treatment for acne and also for improving acne scarring.[2] The efficacy varies depending on the concentration of glycolic acid used -- 30% glycolic acid was sufficient to significantly resolve comedones, papules and pustules,[32] but 35% to 50% glycolic acid did not improve nodulocystic acne, which required 10 sessions of peeling with 70% glycolic acid at 3-week intervals.[33]

Consistent and repetitive treatment with glycolic acid has also been shown to improve acne scars and post-inflammatory hyperpigmentation.[21][32][33][34][35]

Comparative studies indicate that 70% glycolic acid is a better treatment option for acne than Jessner's solution, as it provides equal treatment effects and is better tolerated.[36] By the same reasoning, salicyclic acid peels may be recommended over glycolic acid peels for treating mild to moderately severe acne, for it is just as effective and causes fewer side effects.[37]

The combination of microneedling and glycolic acid peels gives excellent results in the treatment of acne scars.[38] However, combining glycolic acid peels with microdermabrasion at the same session may lead to post-inflammatory hyperpigmentation, and care should be taken for patients with darker skin types.[39]

3.11 Melasma treatment

Melasma is a that common disorder of facial hyperpigmentation that primarily affects females of Hispanic and Asian descent.[40][41] 50% glycolic acid peels improved melasma scores in 91% of patients, in one study on 15 Indian women, with a better response seen in epidermal rather than mixed melasma.[40]

While an early study found that 55% to 75% glycolic acid was less effective than 10% to 15% trichloroacetic acid in treating melasma, more recent comparative studies indicate that 20% to 35% glycolic acid is equally effective as 10% to 20% trichloroacetic acid, and was associated with fewer side effects.[42][43]

Similarly, 70% glycolic acid peels are also as effective as 1% tretinoin peels in improving melasma severity and area, with the added advantage of causing less discomfort to patients.[44][45]

Q-switched neodymium-doped yttrium-aluminium-garnet laser plus glycolic acid peels also seems to be superior to treatment with the laser alone in the treatment of mixed-type melasma.[46]

Glycolic acid has also been successfully used in combination therapy for melasma treatment. A topical regimen of 2% hydroquinone + 10% glycolic acid significantly reduced both melasma and fine facial wrinkling.[47] Serial glycolic acid peels of 30% for the first three sittings and 40% for the next three sittings, combined with the modified Kligman's formula (2% hydroquinone, 0.025% tretinoin, and 1% mometasone) also resulted in greater and more rapid improvement than treatment with the modified Kligman's formula alone with no peeling.[48] Hydroquinone using as a priming agent also enhances the results of glycolic acid peels in melasma while decreasing post-peel post-inflammatory hyperpigmentation.[49]

Formulations containing glycolic acid and kojic acid also seem to be highly effective in reducing pigmentation in melasma patients.[50][51]

Interestingly, a commercial skin brightening system (Lumixyl Topical Brightening System) comprising a 0.01% decapeptide-12 cream, an antioxidant cleanser, a 20% buffered glycolic acid lotion and a broad spectrum SPF 30 sunscreen, has been evaluated in several studies for treating facial melasma. The first of these, a split-face, double-blind and placebo-controlled pilot, significantly improved the appearance of melasma and overall facial aesthetics with high patient satisfaction.[52] Subsequent studies confirmed that the this system accelerates the clearance of mild-to-moderate melasma, without the associated cytotoxicity of hydroquinone.[53][41]

Glycolic acid directly suppresses melanin formation in melanocytes by inhibiting the activity of tyrosinase, the rate-limiting enzyme involved in the production of melanin. It also appears to remodel the epidermis and accelerate its turnover, which would result in rapid pigment dispersion.[54]

4. Side Effects

4.1 Irritation

The glycolic acid peel is time-tested and side effects are largely minor, including erythema, a stinging sensation, mild burning and transient post-inflammatory hyperpigmentation.[2] Due to its acidity, buffered or partially neutralized glycolic acid, which causes less tissue damage than free acid, has been recommended for use.[55]

4.2 Blisters and scarring

Unbuffered glycolic acid may cause erosive blisters and scarring.[43][56] To avoid scarring as well as postinflammatory hyperpigmentation in dark-skinned patients, it is important to avoid facial scrubs, depilatory creams, waxing, bleaching, microdermabrasion, and laser hair removal for at least 1 week before the procedure.[2]

4.3 Increased sensitivity to UV light

Topical application of glycolic acid cream did not change the UV light sensitivity or alter the carcinogenesis of solar-simulated light of mouse skin,[57][58] but did enhance UV-induced skin damage in guinea pigs[59] and sensitize human skin to the damaging effects of UV light, as measured by an increase in erythema, DNA damage and sunburn cell formation.[60][61] Therefore, care is warranted against using glycolic acid excessively or on a chronic basis, particularly in those with photosensitive skin.[59]

Scientific References


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