How do Artificial Sweeteners Trick Our Taste Buds into Thinking They’re Sugar?

The science of taste is confusing. We think of certain foods as having certain tastes. By extension, we think those foods represent those tastes. But our taste buds do not react to foods, they react to food compounds. To explain further, here is my informal answer to a related Quora question: “How do artificial sweeteners trick our taste receptors into thinking they’re sugar?”

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The Simplified Science of Sweetness

Artificial sweeteners do not trick our sweet taste buds into thinking they are sugar.  We do not have taste receptors that detect sugar. We have taste receptors that detect sweetness. So, in other words, our sweet taste receptors do not think artificial sweeteners are sugar, they only think they are sweet (of course they can’t think at all, it’s all just chemical reactions).

The taste cells responsible for detecting sweetness contain receptor proteins that bind to sweet ligands and this causes a signal from activated synapses to sensory nerve fibers that carry the signal to the brain, where the “sweet” taste is processed.

A “sweet ligand” is a molecule that binds to and activates human sweet taste receptors. These types of molecules are not only sugars, but can be many other compounds. Even some amino acids are sweet. For example, glycine is sweet. You can use glycine powder to sweeten your coffee. Some proteins can also be sweet. And, of course, artificial sweeteners are sweet.

Here is a more formal explanation of this process:

Binding of a [sweet] ligand to the sweet taste receptor leads to activation of the heterotrimeric G-protein α-gustducin. Phospholipase C β2 is subsequently stimulated, leading to release of intracellular Ca2+ and activation of the transient receptor potential cation channel M5 (TRPM5). This sequence results in the release of ATP, which can then activate adjacent sensory afferent neurons that send signals to brain centers involved in taste perception. 1

This can be confusing and the science of taste is confusing. Something that is sweet is something that binds to our sweet taste detectors. We think of sugar as the definition of sweet. But we only perceive it as sweet because it binds to these proteins in our sweet taste cells. When other compounds bind to them, they are detected as sweet as well. A compound does not have to be like sugar to do this. Instead, a wide range of compounds are able to bind to the sweet taste receptors and many of these are chemically unrelated to sugars or even carbohydrates in general. Some artificial sweeteners were discovered to be sweet by accident.

For example, when James Schlatter discovered the artificial sweetener aspartame, he wasn’t trying to make an artificial sweetener. He was trying to make an ulcer drug. As the story goes,  he accidentally got some of the compound on his fingers and when he licked his fingers to pick up a piece of paper he noticed a very sweet taste. Wala! A new artificial sweetener (in time).

Here are some sweet compounds:

  • Glucose, fructose, sucrose, maltose.
  • Artificial sweeteners: Saccharin, aspartame, cyclamate.
  • Sweet amino acids: Glycine, D-tryptophan, D-phenylalanine, D-serine.
  • Sweet proteins: Monellin, brazzein, thaumatin.

Of course, some compounds are sweeter than others. For example, fructose is sweeter than glucose or sucrose (sucrose, or table sugar, is half fructose and half glucose).

Artificial sweeteners have such affinity to sweet taste receptors that they can be much sweeter than sugar. For example,  aspartame is approximately 200 times sweeter than sugar so only small amounts are needed to approximate the sweetness effect of table sugar (sucrose). Most of the powder in a small packet of artificial sweetener is dextrose or maltodextrin.

Since artificial sweeteners bind more tightly to our sweet receptors, they also take longer to release, meaning that they have a much longer aftertaste. We detect them more quickly and the taste persists for longer. The bitter aftertaste associated with most artificial sweeteners may mean that they also have some ability to bind to bitter receptors, and there is evidence to suggest this. To understand this, be aware that we have around 25 different bitter receptors and different bitter compounds bind to different ones. This explains why you may be overwhelmed by one bitter flavor and be perfectly happy with another.

Saccharin activates the bitter receptor subtypes TAS2R31 and TAS2R43. On the other hand, the artificial sweetener cyclamate binds to TAS2R1 and TAS2R38. If a compound binds to any of these receptors, it will result in a bitter taste sensation. Interestingly, it’s also known that when saccharin and cyclamate are used together, there is no bitter taste, or at least much less.

This is because while saccharin, while being able to bind to TAS2R31 and TAS2R43, can also block the receptors that cyclamate binds to. And, the reverse is true. While being able to bind to TAS2R1 and TAS2R38, cyclamate blocks  TAS2R31 and TAS2R43! The result is that all you taste is sweet. Each sweetener still binds to sweet taste receptors while blocking the bitter taste receptors associated with the other. 2 This is why the two compounds are often used together (cyclamate is banned in the U.S.) and are sold as a combination in Europe under the brand name Assugrin.

Aspartame and sucralose are both often used in combination with the sweetener acesulfame K (ace K). Ace K works synergistically with these other sweeteners to produce a sweeter, less bitter taste. In this case, the mechanism is different than above, since ace K does not block any of the bitter receptors for aspartame or sucralose, and vice versa.

It may interest you to know that the sweetest compound is a protein called thaumatin (or talin). It comes from the katemfe plant (Thaumatococcus daniellii) in West Africa, and it is around 3,250 times sweeter than sugar. Can you imagine?

Key Summary Points For “How do Artificial Sweeteners Trick Our Taste Buds into Thinking They’re Sugar?”

  • Artificial sweeteners do not trick our sweet taste buds into thinking they are sugar because our sweet taste receptors don’t detect sugar, they detect sweetness.
  • When a sweet ligand binds to sweet taste receptors, this causes a signal from activated synapses to sensory nerve fibers that carry the signal to the brain, where the “sweet” taste is processed.
  • Many different compounds can bind to sweet taste receptors and be perceived as sweet, including sugars like glucose, fructose, sucrose, and maltos, artificial sweeteners like saccharin and aspartame, sweet amino acids like glycine and D-tryptophan, and sweet proteins like monellin and thaumatin.
  • Artificial sweeteners can also bind to bitter taste receptors, causing a bitter aftertaste.
  • When saccharine and cyclamate are used in combination, they can block each other’s bitter receptors, resulting in a purely sweet taste.
  • Aspartame and sucralose are both paired with the sweetener acesulfame K (ace K). Ace K works synergistically with these other sweeteners to produce a sweeter, less bitter taste
  • The sweetest known compound is the protein thaumatin, which is around 3,250 times sweeter than sugar.
References
  1. Lee AA, Owyang C. Sugars, Sweet Taste Receptors, and Brain Responses. Nutrients. 2017 Jun 24;9(7):653. doi: 10.3390/nu9070653. PMID: 28672790; PMCID: PMC5537773.
  2. Behrens, Maik, 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, no. 10, Oct. 2017, https://doi.org/10.1016/j.chembiol.2017.08.004.