Artificial sweeteners can have a not-so-sweet side — a bitter aftertaste. Their flavors can be such a turnoff that some people never use them. Decades ago, people noticed something special about two of these artificial sweeteners:saccharin and cyclamate. Each tastes bitter on its own. But that bitterness disappears when they’re consumed together. At last, scientists know why.
On its own, each sweetener stimulates both sweet and bitter sensations. But when taken together, each sweetener blocks at least some of the other’s bitterness. The result could make your bitter soft drink better. And that could point scientists to the next super sweetener.
Our tongues are covered in receptors. These are molecules that serve as docking stations for certain chemicals. Tongue receptors are specific to various tastes: sweet, salty, sour, bitter and savory (also called umami).
Artificial sweeteners taste sweet because their chemical structure activates receptors on the tongue for sweet taste. Saccharin is 300 times as sweet as sugar. Cyclamate is 30 to 40 times sweeter than the real deal. Saccharin has been in use since its discovery in 1879. It’s best known as Sweet’N Low in the United States. Cyclamate was initially approved in the United States in 1951. But it was banned as a food additive in 1969 over concerns that it caused cancer in rats. It remains popular elsewhere. In fact, it’s the sweetener in Canada’s version of Sweet’N Low.
Yet many artificial sweeteners don’t activate just sweet receptors. Their structures tickle bitter receptors, too. The result is a sweet start but a bitter aftertaste. Saccharin and cyclamate both have bitter ends. In the 1950s, scientists realized that combiningthe two wasn’t nearly as bitter as was either by itself. The mixture is still available in Europe. There, it’s sold under brand names such as Assugrin.
But scientists didn’t know why the combo was such a sweet deal. One reason: Scientists simply didn’t know a lot about how we taste. The receptors for bitter flavors were only discovered in 2000, explains Maik Behrens. He works at the German Institute of Human Nutrition Potsdam-Rehbrűcke. There, he studies molecular biology — the role of molecules that are essential for life.
Over time, 25 different potential bitter-taste receptors have emerged. And science has shown that not everyone has the same levels of each type. That’s why some people may taste the bitterness in greens like broccoli more strongly, while other people are more bothered by artichokes or asparagus.
“A lucky chance”
Behrens and his colleagues Kristina Blank and Wolfgang Meyerhof wanted to find out which bitter-taste receptors saccharin and cyclamate trigger. To do that, the researchers examined the genes — or instructions for making molecules — for the 25 known subtypes of bitter receptors.
Human taste cells are difficult to work with in the lab. So the scientists inserted the taste genes into human kidney cells that were growing in dishes. Each gene came tagged with something called a reporter gene. This is a gene that scientists can look for to find out if it — and the gene it now partners — made it into the kidney cell’s DNA. The reporter gene glowed when the receptors it was in were stimulated. That let the researchers see exactly what was going on inside the cells.
Previous studies of the two sweeteners had shown that saccharin activates the bitter receptor subtypes 31 and 43. Cyclamate tickles subtypes 1 and 38. Stimulating any of those four subtypes will leave a bitter taste in your mouth.
But cyclamate doesn’t just activate the two bitter receptors, Behrens and his colleagues showed. It also blocks the bitter receptors that saccharin stimulates. Cyclamate slips into the space inside those bitter receptors and clogs it up. So with cyclamate around, saccharin can’t get at the bitter-taste receptors it normally triggers, Behrens explains. Bye-bye, bitter saccharin.
The reverse is also true, somewhat. Saccharin blocks subtype 1. That’s one of the bitter receptors that cyclamate turns on. But saccharin doesn’t block the receptor very well. In fact, you would need so much saccharin to completely block cyclamate’s bitterness that the saccharin’s own bitterness would become overwhelming. So it’s probably cyclamate blocking saccharin’s bitter receptors that makes the duo a sweet combination.
Behrens and his colleagues reported their findings September 14 in the journal Cell Chemical Biology.
The researchers also tested whether the combo would boost activation of sweet receptors. Alas, no. In combination, saccharin and cyclamate stayed just as sweet.
“This addresses a longstanding puzzle: why mixing two different sweeteners changes the aftertaste,” says Yuki Oka. “They are interrupting each other at the receptor level.” Oka studies the brain at the California Institute of Technology in Pasadena.
It’s not too surprising that a sweetener might block some receptors and stimulate others, he notes. But that saccharin and cyclamate complement each other so well is a lucky chance. In fact, he adds, “It’s surprisingly beautiful.”
No actual tongues tasted sweeteners in these tests, Oka notes. The tests took place on cells in dishes. And those cells contained human bitter-taste receptors. So it’s likely that the same thing happens when the combo hits a human tongue.
Behrens hopes the cells he developed can be used to predict how other sweeteners might interact. It might help scientists develop new, sweeter flavors. He has money to do this work from a large group of researchers and companies. Many of them will probably be very interested in any sweet results. And along the way, scientists may be able to resolve more taste mysteries of the past.
(for more about Power Words, click here)
activate (in biology) To turn on, as with a gene or chemical reaction.
artificial sweetener A chemical substance that has a sweet taste but few or no calories. People and food manufacturers add artificial sweeteners to foods and drinks to give them a sweeter taste. Many different artificial sweeteners exist. They include saccharin, sucralose and aspartame, among others.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
colleague Someone who works with another; a co-worker or team member.
cyclamate An artificial sweetener initially approved for sale in the United States in 1951. It was banned as a food additive in 1969 over concerns that it caused cancer in rats. It remains popular elsewhere. In Canada, it’s the sweetener in Sweet’N Low.
docking The act of bringing together and inserting one thing into another.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
kidney Each in a pair of organs in mammals that filters blood and produces urine.
marker (in biomedicine) The presence of some substance that usually can only be present because it signals some disease, pollutant or event (such as the attachment of some stain or molecular flag). As such, this substance will serve as a sign — or marker — of that related thing.
mechanism The steps or process by which something happens or “works.” It may be the spring that pops something from one hole into another. It could be the squeezing of the heart muscle that pumps blood throughout the body. It could be the friction (with the road and air) that slows down the speed of a coasting car. Researchers often look for the mechanism behind actions and reactions to understand how something functions.
molecular biology The branch of biology that deals with the structure and function of molecules essential to life. Scientists who work in this field are called molecular biologists.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
neuroscientist Someone who studies the structure or function of the brain and other parts of the nervous system.
nutrition (adj. nutritious) The healthful components (nutrients) in the diet — such as proteins, fats, vitamins and minerals — that the body uses to grow and to fuel its processes. A scientist who works in this field is known as a nutritionist.
receptor (in biology) A molecule in cells that serves as a docking station for another molecule. That second molecule can turn on some special activity by the cell.
reporter gene This is a sequence of DNA that scientists attach to some gene in which they are interested. This new DNA works like a marker to flag that the gene of interest is doing what they want it to do. Reporter genes often glow a certain color, or resist a certain drug. That can make it easy to see what the reporter gene — and the gene to which it’s attached — is up to.
saccharin A no-calorie sugar substitute.
taste One of the basic properties the body uses to sense its environment, especially foods, using receptors (taste buds) on the tongue (and some other organs).
umami One of the five major tastes (along with sweet, sour, salty and bitter). It has been described as savory but most people find the mild flavor hard to characterize. It is particularly prized as a flavor in Japanese cuisines.
Journal: M. Behrens et al. Blends of non-caloric sweeteners saccharin and cyclamate show reduced off-taste due to TAS2R bitter receptor inhibition. Cell Chemical Biology. Vol. 24, October 19, 2017, p. 1199.e2. doi: http://dx.doi.org/10.1016/j.chembiol.2017.08.004.