Salicylic Acid

Salicyic acid, a natural compound found in many fruits and vegetables, has been used for decades to treat various skin disorders and can also help alleviate the signs of aging.

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

Mild

Salicylic peels have been observed to reduce fine lines, and sodium salicylate significantly reduces wrinkle depth.

B

Smoother skin

Mild

Sodium salicylate significantly improves the smoothness of the skin after 4 and 8 weeks of daily application.

C

Warts treatment

Strong

Is an effective cure for common warts. Can be used alone or in combination with cryotherapy, pulsed dye laser therapy, alpha hydroxy acids or prescription medications.

C

Melasma treatment

Moderate

Effective in reducing epidermal melasma in Asian skin and in darker skin types when used as superficial chemical peels.

C

Acne treatment

Moderate

Helps clear acne when used in chemical peelings or as an ingredient in topical products. Also improves postinflammatory hyperpigmentation.

D

Photoprotection

Moderate

Blocks UVA and UVB radiation, reduces the formation of sunburn cells and DNA damage, and suppresses the development of skin tumours.

D

Psoriasis treatment

Moderate

Useful in treating plaque psoriasis and scalp psoriasis, either alone or combined with other topical agents or treatment modalities.

D

Skin lightening

Mild

Salicylic acid peels lightened post-inflammatory hyperpigmentation in acne patients and faded pigmented spots in aged skin.

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Scientific Research


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Table of contents:

1. Sources

Salicylic acid and related compounds are produced by plants to help defend against pathogen attack and environmental stress.[1][2] It was first isolated from the willow in the 1830s, and first chemically synthesized in the 1870s.[3] Dietary sources of salicylic acid include fruit, vegetables, tomato-based juices and sauces, fruit juice, tea, wine, and various herbs and spices.[1][4]

2. Bioavailability

Salicylic acid readily penetrates healthy skin, especially on the cheek, neck and groin area but also on the breast, back, thigh, lower leg and the foot (but not the sole).[5] It penetrates mainly through the transfollicular route.[6]

The vehicle plays an important role in the topical delivery of salicylic acid, with absorptive ointments and collodion formulations delivering a greater amount of salicylic acid across intact skin.[7][8][9] Hydrogels, a microgel, an oleogel and a transdermal patch containing salicylic acid and niacinamide has also been developed.[10][11][12]

Other techniques that have been explored to enhance or control absorption include the prodrug strategy[13], a molecular form technique to prepare supersaturated solutions,[14] iontophoresis,[15][16], ion-pair formation,[17][18] the use of different polymers as emulsifiers,[19][20][21] and the use of penetration enhancers.[22]

Skin in which the stratum corneum barrier is perturbed due to damage by skin irritants or conditions such as psoriasis show even higher penetration of salicylic acid relative to intact, healthy skin.[23][24] Repeated applications of salicylic acid at daily intervals also increases its penetration flux.[25]

The mean plasma concentration of salicylic acid after application of a facial peel containing 30% salicylic acid for 5 minutes is 0.81 µg/ml and reaches a maximum of 56.4 µg/ml after 1.4 to 3.5 hours. These values are similar to that observed when a leave-on product containing 2% salicylic acid is applied.[26] Systemically available salicylic acid is eventually eliminated through the urine.[27]

3. Effects on the skin

Salicylic acid helps exfoliate the skin by promoting desquamation of the stratum corneum.[28] It is often used as a superficial chemical peel to resurface photoaged skin, leading to the fading of pigmented spots, decreased surface roughness, reduced fine lines and the removal of lentigines.[29][30]

Salicylic acid has also been used as an ingredient in topical products to reduce hyperpigmentation and the appearance of dark spots.[31][32]

In addition, sodium salicylate obtained from neutralizing 1% salicylic acid with sodium hydroxide significantly reduced wrinkle depth and skin roughness compared to placebo after 4 and 8 weeks of daily application. Because salicylic acid can irritate the skin, sodium salicylate is especially suitable for individuals with sensitive skin.[33]

Low-dose 5-fluorouracil in combination with 10% salicylic acid has also been shown in multiple studies to be effective in clearing actinic keratoses, a type of skin lesions arising after chronic sun exposure that can develop into skin cancer.[34][35] Significantly, this form of therapy demonstrated superior sustained clinical efficacy compared to the combination of 3% diclofenac + hyaluronic acid, as measured by a lower recurrence rate.[36]

Salicylic acid peels provided no additional benefits in improving hyperpigmentation, skin texture, fine lines, skin dryness, skin tone or skin clarity on the neck and upper chest when used with a cream containing 4% hydroquinone and 2% glycolic acid, however.[37]

In vitro experiments have shown that chemical peeling with 30% salicylic acid dissolved in polyethylene glycol led to a reorganization of the epidermis and a rebuilding of the superficial dermal connective tissue in mice skin,[38] and that sodium salicylate stimulated the synthesis of fibrillin and collagen-1 in human skin in vivo.[33] These may explain salicylic acid's wrinkle effacement effect.

3.2 Photoprotection

Salicylic acid can protect the skin from UV damage. Salicylic acid in petrolatum blocks both UVA and UVB radiation, the main causes of skin aging and sunburn.[39][40] In experiments on mice, topical application of a 4% salicylic acid cream for 6 weeks raised the dose of solar-simulated light required to induce measurable edema from 90 mJ to 137 mJ, an increase of >50%.[41] Salicylic acid has also been shown to inhibit the activity of inflammatory mediators such as COX-1 and COX-2, reduce the formation of sunburn cells and to promote the removal of thymine-thymine dimers in living skin equivalents.[42]

Furthermore, chemical peeling with salicylic acid is associated with reduced expression of the p53 tumour suppressor protein as well as normalization of keratinocyte differentiation,[43] which may explain why it has been demonstrated to suppress the development of skin tumours.[44][45] It has also been suggested that chemical peeling with agents such as salicylic acid may prevent tumour formation by removing photodamaged cells.[46]

Concerns over increased sensitivity to UV radiation following the use of skin care products containing salicylic acid may be unwarranted, as treatment with 2% salicylic acid for 3.5 weeks did not lead to significant changes in erythema, DNA damage or sunburn cell formation.[47] It is not clear whether higher concentrations of salicylic acid or longer periods of treatment will increase photosensitivity, however.

3.3 Melasma treatment

Salicylic acid peels can help improve melasma.[48] Peeling with salicylic acid has been shown to be as effective as peeling with Jessner's solution in reducing epidermal melasma.[49] It is also safe and effective on individuals with darker skin.[50] However, the addition of biweekly salicylic acid peels to a regimen of twice daily application of hydroquinone did not provide extra benefits in the treatment of melasma.[51]

3.4 Acne vulgaris treatment

Salicylic acid is useful in acne treatment due to its anti-inflammatory,[42] keratolytic,[52] comedolytic[53] and bacteriostatic[54] effects. Salicylic acid pads reduced the number and severity of acne lesions in 3 placebo-controlled studies,[55] and a clinical trial on 35 Korean patients with facial acne found that treatment with 30% salicylic acid peels on a biweekly basis for 12 weeks decreased the counts of both inflammatory and non-inflammatory acne lesions.[56] The formulation of 30% salicylic acid in a polyethylene vehicle seems to be especially beneficial for chemical peeling, as it led to the disappearance of comedones and papules with minimal inflammation or other adverse effects such as hyperpigmentation or keloids.[57][58] Salicylic acid peels can also improve post-inflammatory hyperpigmentation, a common sequelae of acne.[59] Full-face peels with 30% salicylic acid biweekly for 3 months successfully lightened postinflammatory hyperpigmentation in the faces of Asian patients with acne.[60]

Salicylic acid appears to aid the treatment of mild-to-moderate acne when incorporated in topical products. A regimen containing a topical blend of salicylic acid + sandalwood oil resulted in notable reductions in acne lesions when used for 8 weeks,[61] and a 1.5% salicylic acid cream improved facial acne in 95% of patients in a separate study.[62]

Salicylic acid may be more effective than benzoyl peroxide in treating acne. In 1 study, patients treated with a 2% salicylic acid cleanser for the first 2 weeks showed a significant improvement in acne due to a reduction in comedones, but their condition worsened when they were treated with a 10% benzoyl peroxide wash over the next 2 weeks.[63] Another study however found 2% salicylic acid + 0.5% chloroxylenol cream to be as effective as 5% benzoyl peroxide gel in reducing papulopustules and comedones.[64]

The effectiveness of salicylic acid + the antibiotic clindamycin has also been evaluated. In a single-blinded clinical trial, treatment of mild-to-moderate acne with a 1% clindamycin + 2% salicylic acid lotion twice daily was significantly more effective than treatment with a 1% clindamycin lotion twice daily, and as effective as treatment with a 1% clindamycin + 0.025% tretinoin lotion once nightly as measured by improvements in the total lesion count and Acne Severity Index.[65]

A meta-analysis of 23 studies involving a total of 7309 patients also revealed that 5% benzoyl peroxide + salicylic acid has comparable efficacy to a combination of benzoyl peroxide + clindamycin in decreasing acne lesions.[66] Moreover, the addition of salicylic acid to treatment with clindamycin phosphate and benzoyl peroxide resulted in significantly better and faster results in diminishing acne lesion counts.[67] Yet another study demonstrated that the combination of salicylic acid + clindamycin phosphate is as effective as tretinoin + clindamycin phosphate in patients with mild to moderate acne vulgaris.[68]

30% salicylic acid peels are at least as effective as Jessner's solution for treating inflammatory and non-inflammatory acne,[53] and had greater therapeutic effect than 50% pyruvic acid peel in reducing facial sebum secretion in acne patients.[69] Further, salicylic-mandelic acid combination peels, a newer treatment modality, is more efficacious on active acne lesions and hyperpigmentation than 35% glycolic acid peels.[70] Peeling with salicylic acid also compared well with peeling with lipohydroxyacid, one of its derivatives.[71] With regards to moderate to severe acne, 20% salicylic acid peels every 2 weeks combined with oral isotretinoin once daily is also more effective than isotretinoin alone.[72]

3.5 Psoriasis treatment

Salicylic acid in gel and foam vehicles have been used to treat psoriasis of the scalp[73][74] and is a treatment option for chronic plaque psoriasis, the most common type of psoriasis characterized by redness, thickness and scaling.[75]

0.1% mometasone furoate + 5% salicylic acid ointment is significiantly more effective than 0.05% flucinonide ointment in managing moderate to severe plaque psoriasis.[76][77] However, although the addition of salicylic acid to treatment with clobetasol propionate is more effective than treatment with a pulsed dye laser alone or treatment with a pulsed dye laser + salicylic acid,[78] a treatment regimen consisting of petrolatum in the morning and 5% coal tar + 3% salicylic acid ointment at night is less effective than treatment with 0.005% calcipotriol twice daily[79] nor does salicylic acid enhance the therapeutic efficacy of dithranol creams when added at a concentration of 2%.[80]

Other psoriasis treatments involving salicylic acid include pulsed dye laser treatment + topical calcipotriol and salicylic acid,[81] as well as the combination of salicylic acid and betamethasone dipropionate.[82][83]

3.6 Warts treatment

Salicylic acid is an effective treatment for common warts, or verrucca vulgaris. In one study, 26% salicylic acid in a polyacrylic vehicle cleared or greatly improved warts in 81% of patients after just 2 weeks of treatment, while patches containing salicylic acid showed a cure rate of 69% in another study.[84][85] The application of salicylic acid for 5 days prior to pulsed dye laser therapy also lowered the number of pulsed dye laser therapy sessions required to achieve complete clearance of common warts.[86]

Several salicylic acid-containing treatments have been investigated for managing plantar warts caused by HPV. In a double-blind, controlled study, monochloroacetic acid crystals + 60% salicylic acid ointment was found to be significantly more effective than placebo, curing 66% of patients compared to only 18% in the placebo group.[87] The combination of 5% imiquimod cream and a 40% salicylic acid pad has also been reported to be effective in treating a large plantar wart in one patient.[88]

As early as 1984, a topical preparation of 30% salicylic acid, 5% podophyllin and 1% cantharidin successfully treated plantar warts in 81 out of 100 children over the course of 6 months to a year.[89] This treatment has been shown to be more effective than cryotherapy, another common method widely used for treating plantar warts.[90]

Salicylic acid alone, however, is not more effective than cryotherapy with liquid nitrogen in clearing plantar warts, and is less effective than cryotherapy in treating common warts.[91][92][93]

Other salicylic acid-containing treatments for warts that have clinical efficacy include the combination of salicylic and lactic acids[94] and the combination of glycolic and salicylic acids in a gel, which may be a good first-line treatment for facial flat warts.[95]

3.7 Xerosis treatment

Salicylic acid does not influence the water content of healthy skin,[96] but it can help improve abnormally dry skin, a condition known as xerosis. An ointment containing 5% salicylic acid + 10% urea (Kerasal) is as effective as 12% ammonium lactate lotion (Lac-Hydrin) in reducing the severity of foot xerosis, as shown in a double-blind clinical study.[97] This may be related to enhanced desquamation, as urea has been shown to improve the keratolytic effect of salicylic acid.[98]

4. Side Effects

4.1 Skin irritation

Salicylic acid is a skin irritant. Fortunately, its irritation potential can be limited by encapsulation in liposomes[99] and by controlling its penetration into the skin.[19] The surfactant system is particularly important in controlling irritancy, with mild nonionic surfactants like isoceteth-20 keeping the barrier intact while cleansing the skin. Another good strategy is to target more salicylic acid to the epidermis and reduce the rate of salicylic acid permeation through the skin through the use of a polyurethane polymer such as polyolprepolymer-15.[19] Neutralizing salicylic acid with sodium hydroxide to produce sodium salicylate also helps make it suitable for sensitive skin without compromising its antiaging benefits.[33]

4.2 May increase photosensitivity

Although the US FDA advises that all exolifants be used with sun protection due to the concern that repeated use may increase the exposure of the epidermis and dermis to UV radiation,[100] treatment with 2% salicylic acid for 3.5 weeks has been demonstrated not to increase the sensitivity of human skin to solar-simulated radiation, unlike a similar treatment with 10% glycolic acid.[47] The effects of higher concentrations of salicylic acid or longer periods of treatment have not been evaluated, however.

4.3 Salicylate intoxication

Salicylic acid toxicity or salicylism can occur from topical application, though this is rare.[101][102] Topical products containing 2% salicylic acid pose minimal risk of adverse systemic effects to patients without extensive skin disorders,[27] but salicylic acid can be potentially lethal to infants and young children who accidentally ingest highly concentrated preparations[103] or who are subjected to prolonged topical application of salicylic acid under occulsion.[104] Adults can also suffer from salicylate poisoning, as shown in the case of an 80-year old woman whose mental status was affected after 6 days' treatment with salicylate containing ointments.[102]

Patients with skin disorders such as psoriasis or ichytosis are also at higher risk of salicylate intoxication, as a damaged skin barrier greatly enhances the absorption of topical salicylic acid.[105] Long-term topical administration of salicylic acid on widespread psoriatic lesions can lead to systemic poisoning,[106][107] including metabolic acidosis,[105][108] respiratory alkalosis, [105] as well as reversible inner ear damage and hearing loss.[108][109]

Individuals with extensive ichytosis, especially smaller children, are also more susceptible to salicylate intoxication, as evidenced by multiple case reports.[110][111][112][113]

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