Artificial Sweeteners

Reading time: 6 – 10 minutes

There are a multitude of alternative sweeteners available on the market today. Some of these, like fructose, contain calories. Others — the so-called non-nutritive sweeteners — do not. While these “artificial” sugars don’t elevate blood glucose like table sugar does (which makes them more appropriate and healthy for diabetics than traditional sugar is), and while the body can’t convert them into fat, they’re not completely free of problems and complications as components of diet.

Artificial sweeteners

Saccharin is the oldest of the artificial sugars that’s still in use today. It was discovered in the late 19th century, completely by chance, when a chemistry student who was working with coal tar derivatives licked his fingers and found they tasted sweet [1]. Saccharin is about 500 times sweeter than sugar, and the human body can’t break it down to provide the cells with energy, which is why it contains no calories. While some research suggests that it can cause bladder cancer in lab rats, no research has linked saccharin to cancer in humans. Saccharin-containing foods once carried warning labels, but scientists have since determined that rats have specific features of their urinary system (which humans lack) that make them susceptible to bladder cancer from saccharine [2]. Warning labels have been removed from foods as of 2000. Sweet’N Low is a brand of artificial sweetener made from granulated saccharin, dextrose and cream of tartar.

Aspartame is another non-nutritive sweetener that was discovered serendipitously by Jim Schlatter in 1965, as he was attempting to synthesize an ulcer drug [3]. Aspartame is a modified dipeptide, whose full name is aspartyl-phenylalanine methyl ester. Equal is an example of an aspartame-based sweetener.

Dipeptide: a small molecule made up of two amino acids, where amino acids are the building blocks of protein.

Like saccharin, aspartame is sweeter than table sugar (by a factor of about 200), and it’s not possible for the human body to break aspartame down, which explains its lack of calories. The reason artificial sweeteners are sweeter than table sugar is that they bind more tightly to sweetness receptors on the human tongue, which then sends a signal to the brain. Chemicals that don’t bind very tightly — like table sugar — send signals of mild sweetness. Chemicals like aspartame and saccharine bind much more tightly, meaning they stay in the sweetness receptor (and continue to trigger signals) for a longer period of time.

The sweetness receptor is a complex called a G-protein coupled receptor comprised of proteins encoded by the genes TAS1R2 taste receptor, type 1, member 2 (TAS1R2) and TAS1R3 taste receptor, type 1, member 3 (TAS1R3) [4].

While there’s no evidence linking aspartame to cancer or other major health problems in most people, it’s not safe for individuals with the disease phenylketonuria (PKU). PKU is a genetic, meaning inherited, disorder in which affected individuals can’t break down phenylalanine. Phenylalanine is one of the amino acids, which are components of protein. Because those with PKU can’t break phenylalanine down, it accumulates in the bloodstream, and negatively impacts brain development in babies and children. Babies with PKU (a disease that hospitals routinely test newborns for) must be kept on a phenylalanine-free diet in order to avoid impaired physical and mental function. Adults with PKU don’t have to follow as strict a diet, but generally benefit from diets with low phenylalanine. Because aspartame contains the amino acid phenylalanine, aspartame-containing foods carry a warning label.

Sucralose is yet another non-nutritive sweetener. Its chemical structure is quite similar to that of table sugar, but key differences (e.g. the presence of chlorine atoms, where table sugar has none) prevent the human body from breaking it down for energy. Like the other non-nutritive sweeteners, sucralose is much sweeter than table sugar. No research has yet linked sucralose to cancer or other major health problems, but as the newest of the popular non-nutritive sweeteners, it may be some time before long-term effects of routine consumption — if there are any — reveal themselves. Splenda is an example of a sucralose-based artificial sweetener.

While there isn’t reason to believe that non-nutritive sweeteners cause cancer, there is some research evidence to suggest that they aren’t as benign as manufacturers claim. Many individuals who use these calorie-free sweeteners do so in an attempt to avoid the weight gain associated with excess sugar consumption, since the body can convert sugar — but not non-nutritive sweeteners — into fat. However, research suggests that there are sweetness receptors in the gut as well as in the mouth [5], and that artificial sweeteners can bind to these receptors. Further, research reveals that when calorie-free sweeteners bind to gut sweetness receptors, physiological responses mimic those expected in the case of sugar binding to the same receptors: the cells take up glucose [6], and the gut releases digestive hormones [7]. In short, it appears that the human body has an ability to sense the sugar — and therefore caloric — content of foods based upon the binding of key nutrients in those foods to receptors in the gut, but that these receptors are fooled (just like receptors in the mouth) by substitute chemicals. This can disrupt the body’s ability to determine whether a given quantity of food is sufficient to meet energy needs [8]. Compare, for example, the quantity of salad necessary to stimulate a feeling of fullness to the quantity of cheesecake necessary to do the same; the average individual consumes a much greater quantity of salad than of cheesecake, because the gut senses the caloric density of the cheesecake and sends satiety signals after consumption of a smaller quantity.

Satiety signal: signal from the gut to the brain that results in a sense of “fullness” or satisfaction.

By disrupting the body’s ability to equate sweetness with calories, it appears that non-nutritive sweeteners can “teach” the body that sugar contains no calories. This can result in consumption of more total calories, which can lead to increased weight gain. In the end, consumption of sugar in moderate quantities may be more compatible with weight-loss or weight maintenance goals than consumption of artificial sweeteners.


  1. Wotiz. The discovery of saccharin. J. Chem. Educ. 1978 55(3): 161.
  2. Whysner et al. Saccharin mechanistic data and risk assessment: urine composition, enhanced cell proliferation, and tumor promotion. Pharmacol Ther. 1996;71(1-2):225-52.
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  3. Mazur, R.H. (1984). Discovery of aspartame. In Aspartame: Physiology and Biochemistry (L. D. Stegink and L. J. Filer Jr., Eds.). Marcel Dekker, New York, pp. 3–9.
  4. Li et al. Human receptors for sweet and umami taste. Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4692-6. Epub 2002 Mar 26.
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  5. Jang et al. Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15069-74. Epub 2007 Aug 27.
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  6. Mace et al. Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J Physiol. 2007 Jul 1;582(Pt 1):379-92. Epub 2007 May 10.
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  7. Kokrashvili et al. Taste signaling elements expressed in gut enteroendocrine cells regulate nutrient-responsive secretion of gut hormones. Am J Clin Nutr. 2009 Sep;90(3):822S-825S. Epub 2009 Jul 1.
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  8. Egan et al. Taste cells of the gut and gastrointestinal chemosensation. Mol Interv. 2008 Apr;8(2):78-81.
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About the Author

Kirstin Hendrickson, Ph.D., is a science journalist and faculty in the Department of Chemistry and Biochemistry at Arizona State University. She has a PhD in Chemistry, and studied mechanisms of damage to DNA during her graduate career. Kirstin also holds degrees in Zoology and Psychology. Currently, both in her teaching and in her writing, she’s interested in methods of communicating about science, and in the reciprocal relationship between science and society. She has written a textbook called Chemistry In The World, which focuses on the ways in which chemistry affects everyday life, and the ways in which humans affect each other and the environment through chemistry.