WHAT IS ARBUTIN?
by Hannah Sivak, PhD
Biochemist
Skin Actives Scientific LLC

Arbutin is one of the many actives we sell as powders, and we also use it as an  ingredient in our skin brightening cream. The mechanism of action of arbutin is through the competitive inhibition of the enzyme tyrosinase, a key enzyme in the synthesis of melanin, although it has been suggested that it may also affect other steps in the synthesis and accumulation of melanin.

Lately I have been receiving emails asking whether our arbutin is "alpha or beta". That confused me a bit because the chemical extracted from bearberry (Artactophylos uva ursi) is called "arbutin", no alpha or beta, although one of the many synonyms is alpha arbutin. To be sure, I looked it up in the Merck index and I found only arbutin.

After several such emails, I finally realized that the question had to do with the glycosidic bond between the glucose residue and the hydroquinone, but I was still surprised that our clients would be interested in stereochemistry of carbohydrates. The answer to this question was (as usual) in a marketing gimmick.

Arbutin is a relatively simple chemical, with a glucose attached  to a hydroquinone.

Both hydroquinone and arbutin have skin lightening properties, primarily because they inhibit synthesis of melanin. But the glucose residue makes a difference: arbutin does not have the side effects that hydroquinone seems to have.  Arbutin also has anti-cancer activity on melanoma cells, apparently by regulating expression of the p53 tumor suppressor and cell apoptosis.

Because of the arrangement of atoms in space, there are two ways in which the D-glucose can  bind to the hydroquinone, this is why we need the "beta" to describe the structure. The alternative is the 'alpha", but bearberry has the biochemical apparatus to make the beta, not the alpha. The alpha can be  made in the laboratory, and it is now marketed as "alpha-arbutin", although this name is misleading.

The way the D-glucose binds to the hydroquinone is very likely to make a difference in the behavior of the chemical. For example, the glucose residues in cellulose (think "paper") are bound by beta glycosidic linkages, while the same glucose residues in starch (think "bread") are bound by alpha glycosidic linkages. As you know, you  can't make bread with cellulose.

It is disingenuous to suggest that a change in structure from a beta glycosidic linkage as in natural arbutin to an alpha (like in the novel chemical) is a big enough difference to make the chemical  stronger in terms of suppression of pigmentation, while at the same time implying that the novel  chemical is as safe as natural arbutin.

Why do we at SAS sell ascorbic acid derivatives but not the "new" arbutin?  For ascorbic acid, most derivatives are esters of ascorbic acid, which will be quickly transformed by enzymes in the  skin to ascorbic acid. In the case of arbutin, the type of sugar and the way it is bound to the  hydroquinone represents a qualitative difference, because enzymes capable of using the beta  glucosyl will not recognize the alpha glucosyl residue.  More and more analogs and derivatives of arbutin will come to the market, e.g. with xylose replacing the glucose but we will not sell them  until exhaustive toxicological data become available.

Just like for preservatives, I like to use chemicals that have been proven to be safe and effective.

For me, novelty in a chemical is not an advantage but a problem.