The Secret of Salted Caramel: Sodium chloride intensifies neural firing in response to glucose

March 17, 2021

The Secret of Salted Caramel: Sodium chloride intensifies neural firing in response to glucose

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Imagine the luxurious taste of salted caramel trickling over an ice cream sundae, oozing out of a chocolate candy bar, or glazing popcorn with a shiny surface of delectable perfection. In 1977, French chocolatier Henri Le Roux struck the perfect balance between sweet and salty in the development of the amber-colored confection exploding in popularity across the United States. But, have you ever wondered why salted caramel is such a heavenly treat for the taste buds? Researchers in Japan found the answer by investigating proteins found in the kidneys and small intestine.

Taste buds located in papillae—tiny bumps on the surface of the tongue—house receptor cells that generate electrical signals known as action potentials in response to sweet, salty, sour, umami, and bitter food molecules. Fiber bundles known as the chorda tympani and glossopharyngeal nerves relay action potentials to the nucleus of the solitary tract for subsequent transmission to the cortex. A group of proteins classified as T1R receptors is responsible for detecting artificial sweeteners or natural sugars like glucose and sucrose. However, in 2003, a study led by Sami Damak found that mice deprived of T1R3s maintained sugar-detecting abilities, thereby suggesting alternate pathways for the perception of sweet compounds. 

Following this discovery, a team of Japanese and American researchers turned their attention to sodium-glucose cotransporters (SGLTs), protein molecules commonly found in nephrons and small intestine mucosa. SGLTs couple the favorable movement of sodium ions with the uptake of glucose molecules into the intracellular space. All the while, sodium-potassium pumps maintain proper ion concentrations inside and outside the cell. Interestingly, the SGLT1 proteins were recently discovered in the inner lining of the mouth. To investigate the role of these proteins in sugar-responsive taste cells, professor Keiko Yasumatsu of Tokyo Dental Junior College and colleagues recorded the neural activity in the chorda tympani and glossopharyngeal nerves of eight to twenty-week old laboratory mice. The researchers prepared glucose and sucrose solutions mixed with sodium chloride (NaCl), a chemical commonly known as table salt. The mice were knocked unconscious through anesthetic injections, and the solutions were applied on their tongues. Then, the mice were treated with phlorizin, a glucoside acting as a competitive inhibitor of SGLTs.

The researchers found that the chorda tympani and glossopharyngeal nerves of the mice fired more frequently in response to glucose-NaCl solutions than pure sugar solutions. All the while, mixtures of table salt and artificial sweeteners, citric acid, quinine, or other taste compounds failed to generate such enhanced activity. Indeed, the combination of glucose and table salt plays a decisive role in sweet taste detection, as the SGLT1 receptors utilize two sodium ions for the transport of one glucose molecule into taste cells. “In the presence of sugar molecules, the increase in NaCl content of saliva allows for the increased generation of action potentials,” Yasumatsu said. Those potentials are transmitted through nerve fibers to the brain, producing the perception of glucose. Even without additional salt consumption, SGLT1 may play a role every time we consume sugars, or more broadly carbohydrates. “Saliva has 5-100 mM NaCl. We may already enjoy carbohydrates with NaCl even when we did not add salt,” Yasumatsu said. 

In addition, the researchers discovered a significant reduction in the neural firing of mice treated with phlorizin, a compound commonly found in apple tree bark. As phlorizin inhibits SGLTs, the results suggest that the cotransporters are instrumental in sweet-sensitive taste cells. To continue their investigation of SGLT1, Yasumatsu and researchers analyzed the relationship between sugar-solution type and mice consumption behavior. Conscious mice were given glucose solutions with and without NaCl. A lickometer with a laser beam mechanism was used to record the mean number of mice licks for the solutions. Mice licked sugar solutions containing table salt more frequently than solutions without salt, suggesting an enhanced preference for glucose in the presence of NaCl. 

Ultimately, the researchers reasoned that sweet-detecting taste cells exist in three major forms depending on T1Rs, SGLTs, or both receptor types. SGLTs may enable nerve activity in response to glucose even in the absence of T1R receptors. This helps explain the findings of the 2003 research study. At the same time, the two sweet receptors may work in conjunction. In the presence of salt, SGLTs may allow for increased glucose detection by the T1R receptors. “SGLT1 mediates the deliciousness of sugars,” Yasumatsu explained.

But, what does this study on mice have to do with humans? While mice look drastically different from people in both size and appearance, they have genomes roughly eighty-five percent identical to that of human beings. As mice have similar organs, nervous systems, and biological development patterns, Yasumatsu believes that her findings allow for the development of hypotheses on sugar detection in the human body.

Now, let’s return to salted caramel. In the world of baking, salted caramel is made with granulated sugar that is boiled into a brownish-colored liquid. Then, butter, heavy cream, and vanilla are added. Next comes the secret ingredient: salt, which is mixed into the bubbling liquid or sprinkled atop the cooled concoction. When the first heavenly bite of caramel enters your mouth, the salivary amylase enzyme and disaccharidases on the taste cell begin to break down the delectable candy. In SGLT-dependent taste cells, the cotransporters provide a pathway for the movement of glucose monosaccharides aided by the sodium ions of table salt. With the help of NaCl, the sweet-sensitive taste cells generate enhanced action potentials retrieved by the brain. “We can enjoy meals when salt is added to all dishes including sandwiches or hamburgers. Carbohydrates plus sodium chloride offers deliciousness in daily life,” Yasumatsu said. 

To sum it up, this is the secret of salted caramel: it is the perfect marriage of sweet and salty that activates SGLT1 proteins for magical perception of the concoction trickling ice cream, oozing out of a candy bar, or glazing popcorn with a shiny surface of delectable perfection. Is your mouth watering yet?

References:

Randall, I. (2020). Why adding salt makes fruit—and candy—sweeter. Retrieved from https://www.sciencemag.org/news/2020/10/why-adding-salt-makes-fruit-and-candy-sweeter

Yasumatsu, K., Ohkuri, T., Yoshida, R., Iwata, S., Margolskee, R. F., & Ninomiya, Y. (2020). Sodium-glucose cotransporter 1 as a sugar taste sensor in mouse tongue. Acta Physiologica, n/a, e13529. doi:10.1111/apha.13529

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