Isn’t that sweet?

Davis Treybig
Five Guys Facts
Published in
5 min readMay 13, 2017

We all love sweets. So, let’s dive into the world of sweetness — what makes something sweet, what is the biology behind sweetness, and what are some of the sweetest compounds on earth?

The History of Sweetness

No real scientific study of sweetness occurred until the early 20th century, after the field of organic chemistry emerged and allowed people to actually study chemical structures.

In 1914, a German scientist named Georg Cohn came up with what is likely one of the first scientific hypothesis regarding sweetness (and taste in general). Cohn proposed that for a molecule to invoke a certain taste, it had to contain some structural motif called a sapophore which produces the taste. He noted that many of the sweet substances known at the time contained either multiple hydroxyl groups, or chlorine atoms, and therefore believed that the sweetness sapophore might have something to do with those structures.

Two scientists expanded on Georg’s theory in 1919, with a more elaborate theory that, for a compound to be sweet, it must contain exactly one each of two specific structural motifs: glucophore and an auxogluc.

After this, not much more was done to advance science’s paltry knowledge of sweetness until about 1963, when Robert Shallenberger and Terry Acree proposed a slightly more rigorous theory: the AH-B theory of sweetness.

The AH-B theory of sweetness posits that, for a compound to be sweet, it must contain exactly a hydrogen bond donor (AH) and a lewis base (B) separated by .3 nanometers. They believed (though had no evidence to prove this yet), that humans’ sweetness receptors matched this layout, and so the closer a compound was to it, the more the compound would perfectly bind with the human sweetness receptors and produce sweetness.

A slight extension of this theory came in 1972, when Lemont Kier suggested there should be a third binding site — the “X” site. Kier noted that among many groups of compounds, there was a correlation between hydrophobicity and sweetness. Thus Kier proposed that for a molecule to be sweet, it should also have a third binding site called “X” which could interact with the hydrophobic site on the sweetness receptor via london dispersion forces.

All this leads up to the most modern theory of sweetness, which extends the AH-B and AH-B-X theories even further, posing that there are up to 8 interaction sites between a compound and a sweetness receptor. This theory is called the multipoint attachment theory, and suggests that the degree of sweetness in a compound relates to which combination of the 8 possible interaction sites the compound actually interacts with.

The Sweetest Compound on Earth

The biggest piece of evidence that supports the MPA theory is that it has helped us find a number of new, extremely sweet compounds.

Scientists rate compounds on a “sweetness scale”, similar to the Scoville scale used to rate spicy foods. Table sugar is the baseline, ranking at 1, and everything else is measured relative to that. For instance, fructose (the sugar compound in fruit) is about a 1.5, while Aspartame (the sugar compound in many diet sodas) is ~200. Note that this is why Aspartame can be considered “diet” or “zero calorie” — it is so sweet that you can use minuscule amounts of it relative to sugar while achieving the same sweetness, resulting in the amount of calories it provides being almost 0.

However, while aspartame and fructose are cool, the MPA theory gave us something a little better: Lugduname.

Lugduname ranks in at approximately 250,000 times more sweet than table sugar. It is perfectly designed to match the human sweetness receptors, and is likely the sweetest compound on earth. So far as I can tell though, it has not yet been approved for human consumption, and so no one has tried adding it to any foods yet.

There are some other interesting facts about the diversity of sweet compounds. Notably, some inorganic compounds are perceived are quite sweet by humans. A good example of this is Lead(II) Acetate. The romans would actually boil wine in lead pots to imbue extra sweetness into their wine, creating a drink they called sapa. It is believed this led to widespread lead poisoning among the Roman aristocracy.

The Sweetness Receptor

Somewhat interestingly, despite the MPA theory of sweetness being proposed in 1991, we actually didn’t know much about the human sweetness receptor until the early 2000s. Finally, a study with mice found that variations in the gene T1R3 produced very different behavior with respect to sweet foods. Further investigation showed scientists that the T1R3 protein forms a complex with a related protein (T1R2) to form a G-coupled receptor that detects sweetness in mammals.

Interestingly though, despite the fact that all mammals share this sweetness receptor formed by T1R3 and T1R2, there are notable differences among mammals in sweetness detection. For instance, new world monkeys do not find aspartame sweet at all, and it is believed that cats can not taste sweetness period.

Sweetness Modifiers

It turns out that sweetness is not just about what you’re eating — some substances can actually change the way sweetness is perceived. For instance, consider Lactisole.

When consumed, Lactisole has strong anti-sweet properties, in that it reduces your ability to taste sweetness. This compound is used by a huge number of food companies to help you better taste other aspects of food besides just its sweetness. For instance, Lactisole is used in virtually all jams, jellies an similarly preserved products which are extremely high in sugar, to help allow the flavor of the fruit to come through and not just be overwhelmed by sugar.

Some other compounds have been found to have similar sweetness reducing properties, such as Gymnemic Acid and Ziziphin from the Chinese Jujube tree.

There are also some other really interesting compounds like Miraculin which don’t just reduce the sweetness you taste, but actually cause sour foods to taste sweet. This compound is the secret behind products like this, which you can order on Amazon. After tasting the Miraculin, you can bite into a Lemon and it will literally taste as sweet as an apple, with no bitterness at all.

While Miraculin is not fully understood, it is hypothesized that it temporarily alters the structure of your sweetness receptors, causing them instead to be activated by bitter compounds.

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Davis Treybig
Five Guys Facts

Early stage investor at Innovation Endeavors, former Google PM