|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|
Clears facial melasma very effectively especially when combined with hydroquinone, with which it has a synergistic effect.
Lightens the skin by chelating copper at the active site of tyrosinase, the enzyme involved in melanin synthesis, and thereby inhibiting its activity.
Thought to prevent wrinkling induced by UV radiation via its iron-chelating and radical-scavenging abilities.
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Table of contents:
Kojic acid is a natural substance produced by many species of fungi, especially Aspergillus oryzae, which is known in Japan as koji. It has a long history of consumption, because it is produced during the fermentation process in the production of a number of foods including miso (soybean paste), shoyu (soy sauce) and sake.
Studies on rats have shown that kojic acid is rapidly absorbed after dermal administration, with occlusion enhancing penetration. Additionally, copaiba oil and the use of nanotechnology-based drug delivery systems also promote permeation.
In a study on 6 Japanese women, applying 1% of a koijc acid formulation on the cheeks led to detectable plasma concentrations of kojic acid. Repeated exposure also appears to increase the levels of kojic acid in the blood, and hence result in higher systemic exposure, than after a single application.
3. Effects on the skin
3.1 Lightening effect
Kojic acid inhibits the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis mainly by chelating copper at the active site of the enzyme, though its anti-melanogenic activity is also associated with increased IL-6 production.
The effect of kojic acid on cultures of skin cells is less clear. One study showed that despite being a potent inhibitor of mammalian tyrosinase, it was unable to reduce pigmentation in intact melanocytes. 2 other studies investigated the melanin content of melanocytes co-cultured with keratinocytes, and one found that the addition of kojic acid did not have any effect, while the other found a 26% decrease in melanin content compared to the control.
In addition, kojic acid significantly reversed the enhanced pigmentation in the epidermal cells of human skin explants exposed to UV light. A topical product containing kojic acid, emblica extract and glycolic acid was also as effective as 4% hydroquinone cream in lightening the skin of 80 patients with mild to moderate facial dyschromia in a double-blind study.
3.2 Melasma treatment
Melasma is a common acquired cause of facial hyperpigmentation that is aggravated by sunlight, pregnancy and the use of birth control pills.
When a cream containing 1% kojic acid was applied daily to 20 melasma patients, a mean 59% improvement in Melasma Area and Severity (MASI) score was observed after 12 weeks. In a split-face study, 2 similar formulations of glycolic acid + hydroquinone and glycolic acid + kojic acid were applied on each half of the face of 39 patients, and were found to be equally effective in reducing pigmentation.
Kojic acid also has a synergistic effect when combined with hydroquinone; in a study on 40 Chinese women, 2% kojic acid in a gel containing 2% hydroquinone and 10% glycolic acid improved epidermal melasma to a greater extent than a similar gel free of kojic acid. Similarly, 1% kojic acid combined with 2% hydroquinone was more effective than 1% kojic acid alone or other combinations of 1% kojic acid, 2% hydroquinone and/or 0.1% betamethasone valerate in reducing melasma area and severity.
3.3 Anti-wrinkle effect
Iron in the skin is thought to play a key role in photoaging, as it catalyses the generation of reactive oxygen species which can contribute to photodamage and wrinkling. Because kojic acid possesses the ability to chelate iron and scavenge radicals, its anti-wrinkling activity has been evaluated in a study on hairless mice. Chronic exposure to solar-simulated UV irradiation for 20 weeks induced wrinkling, epidermal hyperplasia, conversion of adipose tissue into fibrous tissue in the lower dermis, and an increase in the chondroitin/dermatan sulfate content in the upper dermis. Kojic acid prevented wrinkling when applied to the skin of the mice prior to UV irradiation however, and this anti-wrinkle effect was associated with its strong suppression of the UV-induced alterations in the dermis.
4. Side Effects
4.1 Skin irritation
Kojic acid can be irritating to the skin. It is considered to have a high sensitizing potential, and frequently provokes contact allergies or contact dermatitis. As a result, it is considered safe for use in cosmetics only up to a concentration of 1%.
4.2 Potential carcinogenicity
Chronic administration of kojic acid through the diet has been associated with increased hepatocellular adenomas in mice and increased thyroid follicular carcinomas in rats,, giving rise to fears over its cancer-causing potential. A more recent study, however, concluded that 3% kojic acid cream does not initiate nor promote skin carcinogenesis, as it did not induce micronuclei in mouse epidermal cells or lead to the formation of skin nodules when applied to the back of mice. Moreover, systemic exposure to kojic acid in humans after topical application is estimated to be in the range of 0.03-0.06 mg/kg/day, a level that is not thought to pose significant risk of genotoxicity or toxicity to consumers. These findings lend support to the contention that kojic acid is a safe ingredient when used in cosmetics.
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