Sake for your skin

This post explains an intriguing journal article¹ which has led me to begin painting my face every night with a mixture of 1 part sake (Japanese rice wine) to 49 parts water.

It has been observed that in northern Japan, where high amounts of sake are typically consumed, the women have better complexions than women in other areas of Japan.² Additionally, sake has been used since ancient times as a skin care lotion; it evidently improves the skin’s elasticity by increasing collagen, a protein largely responsible for the skin’s ability to return to its initial shape after being stretched. The authors of the paper of interest¹ have determined that the compound α-D-Glucosylglycerol (GG), produced by the yeast during sake production, is at least partly responsible for conferring this benefit. The yeast produce GG from a chemical made by koji, microbes similar to those used during blue cheese production. It is believed that GG, present at a level of about 0.5% in sake when it is ready to drink, helps the yeast survive during the fermentation process by maintaining the proper amount of water within the individual yeast cells.

To understand how GG improves the skin, knowledge of sensory neurons and their receptors is useful. There are different types of receptors embedded in the membranes of sensory neurons that respond to specific stimuli. Mechanoreceptors respond to stretch and pressure, photoreceptors respond to visible light, thermoreceptors respond to varying levels of heat, and chemoreceptors respond to chemical stimuli. Chemoreceptors are the most relevant to this discussion. It is worth noting that sensory neurons themselves do not actually “sense.” Rather, they receive information and in certain situations pass it along to the appropriate area of the brain for interpretation. When information reaches the right place in the brain, sensory stimuli are sensed, or consciously received. For instance, sweetness is tasted not just because sugar (or a sugar substitute) is bound to the appropriate chemoreceptors on the sensory neurons of the tongue, but because the neurons transmit the stimulus to the brain where it is interpreted as sweet.

Other sensory stimuli are received without conscious awareness but are still very important. For example, sensory neurons in the brainstem help control breathing using chemoreceptors to monitor the pH of the blood as follows: Cells in the body use oxygen when they make energy, and carbon dioxide is released as a byproduct of the energy-making process. Carbon dioxide reacts with water in the blood to increase the blood’s acidity, thereby lowering its pH. When chemoreceptors on sensory neurons in the brainstem are stimulated by such a drop in pH, breathing becomes deeper and more frequent. This increases oxygen uptake and carbon dioxide removal, raising the blood’s pH until the chemoreceptors are no longer stimulated and breathing is stabilized. All of this happens without causing any noticeable sensation in the body, demonstrating that effectiveness does not depend on conscious awareness. I mention this because when I apply the diluted sake to my face it feels just like water. There are a lot of gimmicks on the market that make your skin feel warm or tingly, but don’t be fooled, strange sensations do not mean that the product is doing your skin any good!

When a certain chemoreceptor (vanilloid receptor-1) is stimulated, sensory neurons release small molecules called calcitonin-gene related peptide (CGRP). CGRP is similar to protein except that it is made of a shorter chain of amino acids. Past experiments have shown that, on normal mice, application of GG to the skin leads to increases in collagen and insulin-like growth factor-I (IGF-I), a protein that increases collagen synthesis and is important for maintaining healthy skin. However, on mutant mice which are unable to produce CGRP, the application of GG does not increase collagen or IGF-I. In other words, the collagen and IGF-I boosting effects of GG application depend on the sensory neurons’ ability to release CGRP. With this in mind, the researchers deduced that GG probably acts by stimulating vanilloid receptor-1 on sensory neurons. Then they performed four experiments to further investigate the mechanism of action and effects of GG.

In the first experiment, performed using freshly sacrificed mice, the researchers extracted bulging areas of nerves (called dorsal root ganglia, or DRGs) from just outside the spinal cord. DRGs contain thousands of sensory neuron cell bodies. The DRGs were kept in conditions that would allow them to grow for five days, and then incubated for thirty minutes with either plain media or media containing various concentrations of GG. The researchers found that for the concentrations of GG they tested, the higher concentrations of GG used during the incubation resulted in more CGRP produced by the neurons. Additionally, the researchers used capsazepine (CPZ), a chemical that inhibits vanilloid receptor-1 activation, to verify that the increase in CGRP was caused by activation of vanilloid receptor-1. CPZ on its own had no effect on the baseline CGRP level (without any GG), but it successfully prevented GG from increasing the CGRP level when it was added.

In the second experiment, plain salt water or solutions containing various concentrations of GG were applied to the backs of shaved mice. Half of the mice were normal and half were mutants that could not produce CGRP. Thirty minutes later, the mice were sacrificed and their skin was tested for CGRP, IGF-I, and IGF-I mRNA. mRNA is basically a copy of DNA that is used by the cell to manufacture specific proteins. In this case, the mRNA of interest would be used to manufacture IGF-I. Obviously, the mutant mice did not produce any CGRP, regardless of the application of GG. As expected, however, the normal mice produced more CGRP when GG was applied. The IGF-I levels did not change at all in the mutant mice, but increased when GG was applied to the normal mice. The maximal increase of IGF-I levels occurred when a 0.01% GG solution was applied. Additionally, GG had no effect on IGF-I mRNA levels in mutant mice, but increased IGF-I mRNA in normal mice.

The third experiment began with the application of either plain salt water or a solution containing GG to the backs of live normal and mutant mice. Fourteen days later the mice were sacrificed, and their skins were tested for the amount of collagen they contained. Collagen levels in the skin of normal mice were approximately 20% higher following the application of the GG solution as compared to the control solution. The collagen levels of all mutant mice matched those of the normal mice treated with the plain salt water solution.

Finally, the fourth experiment was done on women. Half of the women received a solution containing 0.01% GG, and the other half received plain salt water as a placebo. Once a day the women applied the solution to their face. This experiment was double-blinded; neither the subjects nor the experimenters knew which solution was given to the subjects. After fourteen days the women’s cheek skin elasticity was measured by pulling the skin away from the face using a vacuum, and then measuring how close to its original position it returned when the vacuum was removed. As the researchers suspected, the women who had been applying the solution containing GG had significantly more elastic skin.

The results of these experiments clearly demonstrate the positive effects of GG on the skin, and support the hypothesis that GG acts by stimulating vanilloid receptor-1 on sensory neurons. Since the results in the second experiment showed the greatest increase in IGF-I when a 0.01% GG solution was applied to the mice, and the fourth experiment showed that a solution containing this concentration effectively increased skin elasticity in humans, I decided to dilute my sake to obtain a GG solution of this concentration. Recall that fully prepared sake has a GG concentration of 0.5%. That means I must dilute 1 part sake in 49 parts water to achieve a 0.01% GG solution.

References:
[1] Harada N., Zhao J., Kurihara H., Nakagata N., Okajima K. “Effects of Topical Application of α-D-Glucosylglycerol on Dermal Levels of Insulin-like Growth Factor-I in mice and on Facial Skin Elasticity in Humans.” Bioscience, Biotechnology, and Biochemistry. 74.4(2010): 759-765. Web.

[2] Nakahara M, Mishima T, Hayakawa T. “Effect of a Sake Concentrate on the Epidermis of Aged Mice and Confirmation of Ethyl Alpha-D-Glucoside as its Active Component.” Bioscience, Biotechnology, and Biochemistry. 71.2(2007): 427-34. Web.