Daisy rose, smiling faintly, and went to the table. “Open the whiskey, Tom,” she ordered, “and I’ll make you a mint julep.”
—From The Great Gatsby by F. Scott Fitzgerald
The spectators at the Kentucky Derby often sate their thirst with mint juleps, a mixture of bourbon, ice, sugar and mint. That mint component of the drink is a natural source of menthol, a key ingredient in Bengay. Bengay takes advantage of menthol’s cooling properties, because the sensory effect of menthol is cool, while other materials such as capsaicin and mustard oil are perceived as hot. And in fact, menthol is among the most important cooling ingredients in cosmetics and is one of the few materials with an immediately detectable impact. So how does it work?
Extensive information on menthol’s use in fragrance and flavor is available in an account from Leffingwell1.
Menthol has stereospecific isomers, meaning the same molecule can have a mirror image with different properties, similar to the relation of your left hand to your right hand. Nature usually makes the left-hand molecule of menthol, which is critical for its activity. The right-hand menthol molecule—or a mixture of right- and left-handed isomers, called “racemic”—won’t work. So when using synthetic menthol, it is important to know its “handedness.”
Biologically active hot and cold molecules work by binding to receptor sites on sensory neurons, cells that send messages to the brain. Looking at these receptors in detail explains the difference in people’s response to temperature and certain chemicals.
You know when you go outside if it is hot or cold. Receptors in the skin detect temperature and send a message to the brain. Important to sensory response is a transient receptor potential (TRP) cation channel that acts as a transduction channel. Transduction means the receptor takes one signal—it could be a sensation of hot or cold, the smell of a rose or any number of things—and turns it into a message for the brain.
Messages are sent along the nervous system by positive ions (cations), which are the biological equivalent of the electric current that turns on a light bulb. The full name of the menthol receptor, TRPM8, means “transient receptor potential cation channel subfamily M member 8.”
When the temperature is above 43°C, the TRPV1 receptor is activated. It activates a surface pore that causes calcium ions to flow into the cell. This causes an electrical change in the cell, which sends a message to the brain that it is hot outside. Capsaicin also binds to this receptor and thus sends a signal to the brain that says “hot.” When the temperature is in the range ~8–28°C, the TRPM8 receptor tells the brain “cold.” Menthol also binds to this receptor and sends the same cold message.
Menthol has more biological activities than just its cooling sensation though. It has analgesic properties due to its activation of some κ-opioid receptors, and this can make the skin less susceptible to the feeling of a sting or rash. Menthol also is an antipruritic, which means it can help treat an itchy scalp.
Put simply, menthol can interact with several receptor areas in the body, and scientists have decoded many of the detailed mechanisms to explain exactly what is happening in these interactions. The effects of menthol are real and well understood.
For beauty and personal care applications, menthol typically has a strong initial effect on the skin and then fades. However, manipulating the molecule to have a milder initial impact but to continue its release over time has long been a desired variant, and a typical approach to this is converting menthol to an ester, which breaks down over time. Menthyl lactate is a common example, and Symrise has commercialized a number of these esters. A recent example is Frescolat X-cool (INCI: Menthyl Ethylamido Oxalate), which the company claims is 82% stronger than its other cooling agent, menthyl lactate. It also is said to be gentle to the skin and has no unpleasant odor.
Another aspect of menthol that can be seen as an interesting trick is its use in the creation of an eutectic mixture—turning two solids into a liquid at room temperature under precise conditions. Eutectic mixtures are familiar to those working with metal alloys, but are much less familiar to those in the beauty industry.
One hundred percent of each separate component is represented on the right and left sides. As blends are created, the melting point drops, meeting at a minimum somewhere in the middle. If this temperature is below room temperature, the result is a liquid. At a molecular level, a eutectic mixture will form when the two components are close enough in structure to dissolve in each other but different enough to disrupt the crystalline structure, lowering the melting point.
One such eutectic menthol mixture has been patented by Sino Lion,2 and consists of a precise ratio of menthol and menthyl lactate. The benefit of this product includes easier handling and the ability to encapsulate the liquid for controlled release in products such as toothpaste.
More Than Menthol
Many other ingredients that provide a sensory impact are also known. For example, Wilkinson Sword did extensive work in the 1970s resulting in two carboxamides with cooling capabilities being marketed, WS-3 and WS-23.
Materials reacting with the hot receptor TRPV1 (vanilloid receptor) have been studied almost as much as the menthol receptor, too. Vanillyl butyl ether (SenseHot from Sino Lion, Hotact VBE from Takasago) is an example. It creates hot sensory effects at levels as low as 0.05%. Pepper spray, based on oleoresin capsicum, is a nasty type of such chemistry. And vanillyl butyl ether can be added to lip products for tingle and plumping, with Smashbox’s O-Plump Intuitive Lip Plumper as one example.
Heating and cooling agents can also be combined, as in Mintiva Heat Therapy, which contains 3% menthol and 0.04% capsicum. Another mixture is seen in Kenneth Cole Reaction Deodorant, which contains menthyl PCA, menthyl lactate and vanillyl butyl ether.
The compounds considered here are some of the classics of what can be glamorously termed neurocosmetics, and there are many ingredients that can interact with the nervous system to provide sensory benefits. The old standby menthol has a characteristic odor that is not present in many other materials, and the intensity, time of release and irritation potential can all be tuned through clever molecular engineering.
Everyone on product development teams should stay abreast of developments in this area, as they have the ability to give instant impact to consumers and send a message that the product is really doing something.
- www.leffingwell.com/menthol1/menthol1.htm (Accessed Apr 5, 2012)
- E Su and CG Wang, Pat US 6,897,195 B2, Composition of Menthol and Menthyl Lactate, Its Preparation Method and Its Applications as a cooling Agent. (2005)
Steve Herman is president of Diffusion LLC, a consulting company specializing in regulatory issues, intellectual property, and technology development and transfer. He is a principal in PJS Partners, offering formulation, marketing and technology solutions for the personal care and fragrance industry. He is an adjunct professor in the Fairleigh Dickinson University Masters in Cosmetic Science program and is a Fellow in the Society of Cosmetic Chemists.