The multitude of colors in our skin—from basic skin tone to freckles, birth marks, and age spots—are created by pigments collectively called melanin, which is produced by organelles called melanosomes within melanocyte skin cells. The main enzyme involved in melanin production is tyrosinase. Skin color varies between individuals based on:254-255

  • Genetics and race, which determines how many melanosomes are in each melanocyte, the number of melanocytes, and how and where they are distributed in the skin layers.
  • Environmental factors that affect pigment production in the skin.

The primary environmental influence on skin pigmentation is sun exposure. Ultraviolet radiation (UV) from the sun stimulates melanin production by activating the tyrosinase and other enzymes in melanocytes, as well as causing DNA damage that affects how melanin is distributed in the skin.254-255

There aren’t many people, especially women, who are happy to find the visible evidence of sun and free radical damage showing up as dark spots on their skin as they get older—hence the multitude of skin lightening agents on the market. These hyperpigmented areas (e.g., age or liver spots, freckles, and melasma) can also occur when skin heals from acne and even cosmetic treatments such as peels and laser resurfacing, but the root cause is thought to be dysfunctional regulation of melanin production in the skin.256

As safety concerns over commonly used hydroquinone have been raised, cosmetic companies have become increasingly interested in finding other natural skin lighteners. Flavonoids are natural chemical compounds in plants that have biological effects on humans and animals—many of them modern scientists are discovering as beneficial. Belonging to the stilbene subgroup of flavonoids, resveratrol can mildly inhibit tyrosinase, the enzyme which skin pigment cells produce that in turn controls melanin. Piceatannol, a derivative compound of resveratrol, has been shown to inhibit pigmentation caused by UV light exposure (as in sunlight), believed to be attributable to resveratrol’s potent antioxidant effects.256

How Does It Work?

In general, skin lighteners work by one or more mechanisms:

  • Reducing production of tyrosinase enzymes.255
  • 250
  • Increased shedding of the upper layer of dead skin cells to remove excess melanin.255
  • Spreading the melanin thinner by regulating the MITF genes that produce proteins which help move melanin from melanocytes to other skin cells.255
  • Degrading existing melanosomes.255

Resveratrol appears to work by inhibiting tyrosinase, MITF, and DCT activity.257

Evidence of Benefit

Lab studies indicate that resveratrol directly inhibits the tyrosinase enzyme and also blocks it from maturing and becoming functional.257 Recently published results on a resveratrol derivative (5HNB) showed significant tyrosinase inhibition. In fact, 5HNB was far more potent than the commercially-used skin lightener kojic acid.258

In an animal study, dark-skinned swine treated with a topical application of 1% resveratrol showed significant skin lightening effect. Further placebo-controlled studies demonstrated that animals treated with topical resveratrol (both before and after UVB exposure) had significantly less skin-darkening than untreated animals exposed to UVB.259

A number of different botanical substances that contain resveratrol and resveratrol analogs, isomers, or derivatives have been lab-tested for their skin lightening effects. The plants that have shown the most powerful skin lightening effects include:

Common Name Scientific Name Plant Part Used Resveratrol or Derivative
Breadfruit260 Artocarpus incisus261 heartwood261 4-prenyloxyresveratrol261
Monkey Jack260 Artocarpus lakoocha262 heartwood261 4-prenyloxyresveratrol261
White or Russian Mulberry260 Morus alba261 roots, stems, leaves263 oxyresveratrol261

Oxyresveratrol, an analog of resveratrol, has been shown in studies to have the greatest lightening effect. Two separate clinical studies demonstrated oxyresveratrol’s skin whitening potency:264

  • Sixty women were divided into groups and applied a test sample of either licorice, kojic acid, or oxyresveratrol extract from A. lakoocha on one arm. After only four weeks the participants who used the oxyresveratrol showed visible skin lightening (compared to the untreated arm), while the kojic acid and licorice-treated participants had lightening after six and ten weeks. The oxyresveratrol produced greater lightening effects than both kojic acid and licorice overall from the fourth week on.
  • In a 1% lotion form oxyresveratrol from A. lakoocha demonstrated faster and greater skin bleaching than a 1% licorice lotion in a clinical study involving 50 women.

Clinical studies, performed by manufacturers, of skin lighteners containing resveratrol (or resveratrol derivatives) have shown promising results as well:

Studies Reported by Manufacturers
Product Name

Also used in Crème à la VITISIN®

“Grapevine Root Extract from the wine region of Bordeaux”
  • More potent than kojic acid.
Inhibited tyrosinase activity between 80-97.5%, depending on concentration.

Clinical studies showed significant reductions in size and pigmentation of age/sunspots after 28 days using Crème à la VITISIN®.

A majority of panel participants using Crème à la VITISIN® users noted skin lightening effects.

“a ‘bright idea’ for your new skin formulation’
  • Pure trans-resveratrol extract to add to skin care products.
  • Even skin whitening.
  • Works quickly.
  • Free from emodin and pesticides.
In a 90 day blinded placebo-controlled clinical study involving 52 women with darker-skin tones, twice daily application of REGU®-FADE resulted in significant skin lightening.

A shorter blinded, placebo-controlled study involving 12 Caucasians showed significant skin lightening when REGU®-FADE was applied three times a day for 14 days.
G.M. Collin Phytowhite Cream
  • Controls overproduction of the skin pigment melanin.
  • Evens skin tone.
  • Moisturizes while reducing dark sun and age-spots.
Company reports clinical tests that showed 71% increase in skin lightening as well as significant moisturizing and smoothing effects.

Other skin lightening products that contain resveratrol:

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Specifically, production of eumelanin.
Skin pigment.
Genes that make dopachrome tautomerase enzymes.
Genes that make microphthalmia-associated transcription factors.
Equal to or stronger than kojic acid.
Probably due to concerns over mixed test results suggesting
possible toxic effects on DNA.
Eumelanin and pheomelanin.

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