In a 2004 study, Mexican researchers tested a 5% ascorbic acid lotion against a 4% hydroquinone lotion in people with melasma. Both lotions markedly lightened the darker areas of the skin. Hydroquinone worked slightly better and gave results in one month while it took three months for the vitamin C lotion to lighten the skin. On the other hand, only one of the 16 patients complained of side effects from the vitamin C lotion as compared to 11 out of 16 for the hydroquinone lotion.
A Japanese study tested whether a fat-soluble form of vitamin C (tetra-isopalmitoyl ascorbic acid) can prevent UV-induced darkening of the skin. They exposed the forearms of the participants to UV radiation (1.5 times the amount it takes to cause a minor sunburn) and applied either a 3% vitamin C or control lotion immediately after the exposure. The vitamin C treated site showed about 13% less darkening than the control site.
Another Japanese study demonstrated 10% magnesium L-ascorbyl-2-phosphate (MAP) produced good or moderate lightening of melasma and liver spots in 19 out of 34 participants.
A 2013 study showed that silicone gel with vitamin C somewhat improved healing of surgical scars; the scars treated with the vitamin C gel showed less hyperpigmentation and color difference from the surrounding skin.
A Korean study showed that a superficial chemical peel combining alpha-hydroxy acid and vitamin C (as ascorbic acid) reduced hyperpigmentation in melasma patients. Unfortunately, I couldn’t find out the concentration of vitamin C. The study looked at this product from Korea.
Herndon et al. showed the combination of 30% vitamin C (as tetrahexyldecyl ascorbate) and 0.5% retinol lotion reduced hyperpigmentation roughly 10% in 12 weeks.
In 2009, Hwang et al. showed that 25% vitamin C (as ascorbic acid) lotion reduced melasma in 16 weeks. I don’t have access to the full-text version of this paper and can’t share with you how much things improved.
In 2013, Journal of Drugs in Dermatology published a paper testing two concentrations of retinol, 0.5% and 1%. The cream with 1% retinol showed good results in reducing signs of aging and hyperpigmentation, but people complained about the side-effects. The 0.5% retinol cream showed modest improvements in skin aging and hyperpigmentation but caused only minor side-effects. Products used in the study: https://www.skinstore.com/p-9841-retriderm-vitamin-a-serum-ultra.aspx
Another study tested the efficacy of 0.1% retinol on photodamage and skin aging. The participants applied 0.1% retinol moisturizer (active treatment) on one side of the face and an identical moisturizer without retinol on the other side. After eight weeks, the side treated with the retinol moisturizer showed about 50% better improvement in hyperpigmentation, wrinkles, fine lines, and overall photodamage.
Kikuchi et al. tested a 0.075% retinol cream and a placebo cream in a split-face study on middle-aged Japanese women. The results showed a reduction in wrinkles and hyperpigmentation in the retinol-treated side as compared to the placebo-treated side. The retinol-treated side also showed slightly more redness and scaling, but these disappeared during the study.
A study on Japanese women showed that 5% nicotinamide moisturizer reduced hyperpigmentation by nearly 25% vs. 15% reduction with a placebo moisturizer.
A large study of 246 Indian women showed a significant reduction in hyperpigmentation with a moisturizer containing 4% niacinamide, 0.5% panthenol, 0.5% vitamin E (as tocopheryl acetate), sunscreen, and glycerin. The moisturizer also improved skin tone and texture and lightened the skin.
Another large study showed that the combination of 4% niacinamide and 2% N-acetyl glucosamine (NAG) with SPF 15 was more effective than an SPF 15 sunscreen alone in reducing hyperpigmentation and improving skin tone. This was a follow-up study of another study from 2007 that showed similar results.
One study compared 4% hydroquinone (HQ) to 4% nicotinamide in people with melasma, a condition similar to post-inflammatory hyperpigmentation. 55% of the participants treated with hydroquinone showed good to excellent results vs. 44% of patients treated with nicotinamide. 18% in the HQ group complained of moderate side-effects whereas 7% in the nicotinamide group complained of mild side-effects.
Castanedo-Cazares et al. compared 4% nicotinamide and 0.05% desonide (corticosteroid) on persistent PIH in a colored skin. The desonide group showed slightly better results with 12% showing excellent, 18% good, 31% moderate, and 37% mild response; the corresponding figures in the vitamin B3 group were 12% excellent, 12% good, 43% moderate, 31% mild. In contrast, 90% treated with a placebo showed poor to mild response.
An Egyptian study asked 20 women to apply a 2% liquiritin (a substance found in licorice flavones) cream on one side of the face and a placebo cream on the other side. 80% of the women showed excellent results in the licorice-treated side vs. none in the placebo-treated side.
A Pakistani study from 2009 compared the effectiveness of 4% liquiritin, 2% liquiritin, and 4% hydroquinone on melasma patients. Their results showed that 73.3% of patients treated with hydroquinone improved vs. 96.7% and 86.7% of the patients improved in the 4% and 2% liquiritin groups. The researchers concluded that liquiritin was both more effective and safer than hydroquinone.
Licorice extract is a mixture of many substances. These studies used a part of a single substance found in licorice extracts. Which makes me skeptical that you could get the same results with creams that contain licorice extract.
Two studies have looked at treating PIH with soy extracts. One showed an average reduction of 12% in 14 out of the 16 participants. Another study showed a significantly better reduction with SPF 30 sunscreen containing soy than with the SPF 30 sunscreen alone.
One study showed deoxyarbutin has minor skin lightening effects. Prior to treatment, the participants spent 10 to 20 minutes per day in a tanning bed for seven days. The tanned areas where then treated with 3% deoxyarbutin cream (DA), 4% hydroquinone cream (HQ), or nothing (control). After five weeks 44.6% of the tan remained in the untreated control area vs. 37.3% in the DA treated area and 51.6% in the HQ treated area. Deoxyarbutin accelerated the fading of tan whereas hydroquinone hindered fading.
In another study a 3% deoxyarbutin lotion was tested as a skin lightener and treatment for liver spots in Caucasian and dark skinned participants. The results showed skin lightening in Caucasians but not on the darker skinned participants while the liver spots improved in both groups.
A split-face study compared a 2% hydroquinone lotion to a 2% kojic acid lotion in patients with melasma, both lotions also contained 5% glycolic acid as penetration enhancer. Both lotions produced a similar reduction in skin pigmentation; the kojic acid lotion was more irritating.
Multi-ingredient cream vs. hydroquinone
A study compared a 4% hydroquinone cream to a multi-ingredient cream. Both the hydroquinone and multi-ingredient creams reduced hyperpigmentation by about 20% over 12 weeks. Both creams caused only mild side-effects.
The multi-ingredient cream was formulated to address the mechanisms behind hyperpigmentation and contained the following ingredients:
- Tetrahexyldecyl ascorbate (an oil-soluble form of vitamin C)
- Linoleic acid
- Glabridin (licorice extract)
Licorice extract + belides + emblica vs. hydroquinone
Another study compared 2% HQ to a multi-ingredient cream with 7% licorice extract, belides (from daisies), and emblica (Indian gooseberry). Medical examination showed improvements in 78% of the participants in the multi-ingredient group and 89% in the HQ group. Two people in the multi-ingredient cream group and seven individuals in the HQ cream group complained of mild side-effects.
Kojic acid + emblica + glycolic acid vs. hydroquinone
Yet another multi-ingredient cream was compared to 4% HQ. This time, the cream contained kojic acid, emblica extract, and glycolic acid. The effectiveness of the multi-ingredient formulation was comparable to the HQ cream.
Salicylic acid + ellagic acid vs. hydroquinone
Another comparison study pitted a 4% HQ cream against a cream containing 0.5% ellagic acid and 0.1% salicylic acid. Ellagic acid is a natural antioxidant found in many fruits and vegetables. Both creams were equally effective in reducing hyperpigmentation and dark spots.